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Literature search results 

Search completed for: 

Search required by: 2 December 2011 

Search completed on: 8 December 2011 

Search completed by: Richard Bridgen 

Search details 

Investigation and management of thrombocytopenia in pregnancy. 

Resources searched 

NHS Evidence; TRIP Database; Cochrane Library; AMED; BNI; CINAHL; EMBASE; MEDLINE; 

Google Scholar 

Database search terms: thrombucytopaenia; exp THROMBOCYTOPENIA; 

thrombocytopen*; thrombopen*; “low platelet count”; pregnan*; exp PREGNANCY; labor; 

labour; childbirth; “child birth”; gestation; gravid*; trimester*; pre-eclampsia; eclampsia; 

exp ECLAMPSIA; investigation*; dianos*; management; MANAGEMENT; treatment*. 

therap* 

Google search string: (thrombocytopenia OR thrombocytopenic OR thrombopenia OR 

FNAIT OR TTP OR ITP) (pregnant OR pregnancy OR foetus OR fetus OR fetal OR foetal) 

Summary 

There is a great deal of research into thrombocytopenia, its subtypes and pregnancy, even 

within the last three years. I have included foetal and FNAIT research as this relates to 

pregnancy but have omitted those papers dealing with purely neonatal 

thrombocytopenia. I hope you find it useful. 

1

Guidelines 

British Committee for Standards in Haematology 

Guideline on the investigation and management of adults and children presenting with 

thrombocytosis 2010 

ET is the commonest MPN in women of childbearing age and a significant number of 

pregnancies have been described in the literature, but these data do not enable confident 

management guidelines to be drawn up. A summary and suggested algorithm for 

pregnancy management in ET 

European Society of Cardiology 

Guidelines on the management of cardiovascular diseases during pregnancy 2011 

Heparin-induced thrombocytopenia is markedly lower with LMWH than with UFH as is 

heparin-induced osteoporosis (0.04%).24 

Finnish Medical Society Duodecim 

Thrombocytopenia 2007 

New South Wales Health 

Maternity - management of hypertensive disorders of pregnancy 2011 

1. If features of preeclampsia are present, additional investigations should include: 

If there is thrombocytopenia or a falling haemoglobin, investigations for 

disseminated intravascular coagulation (coagulation studies, blood film, LDH, 

fibrinogen). 

2. Thrombocytopenia is the commonest hematologic abnormality seen in preeclampsia; 

the lower limit of the normal platelet count in pregnancy is approximately 140x109/L 

but the risk of spontaneous bleeding is not significantly increased until the count falls 

below 50 x 109/L. Even so, there are concerns with central neuraxial anaesthetic and 

analgesic techniques at higher levels (50-75 x 109 /L), and surgical bleeding may be 

increased even with moderate thrombocytopenia… 

NICE 

CG107 Hypertension in pregnancy 2011 

1. Chlorothiazide may carry the risk of congenital abnormality, neonatal 

thrombocytopenia, hypoglycaemia and hypovolaemia. 

2. Neonatal thrombocytopenia and bleeding secondary to hydralazine ingestion 

throughout the 3rd trimester have been reported in 3 infants. This however may have 

been due to maternal hypertension. 

CG92 Venous thromboembolism - reducing the risk 2011 

Fondaparinux + GCS was the most cost-effective strategy when heparin Induced 

thrombocytopenia was considered. 

Royal College of Obstetricians and Gynaecologists 

Thrombosis and Embolism during Pregnancy and the Puerperium, Reducing the Risk 2009 

1. Danaparoid is a heparinoid that is mostly used in patients intolerant of heparin, either 

because of heparininduced thrombocytopenia or a skin allergy to heparins…The 

experience in the use of this agent in a total of 51 pregnancies was reviewed… There 

were four maternal bleeding events, two of which were fatal owing to placental 

problems (praevia and abruption)…There were no adverse fetal outcomes attributed 

to danaparoid. 

2

2. Lepirudin. Its use is best avoided in pregnancy unless there is no acceptable 

alternative. 

Thromboembolic disease in pregnancy and the puerperium: acute management 2007 

Pregnant women who develop heparin-induced thrombocytopenia or have heparin allergy 

and require continuing anticoagulant therapy should be managed with the heparinoid, 

danaparoid sodium or fondaparinux, under specialist advice. 

SIGN 

Prevention and management of venous thromboembolism 2010 

2.9.1 heparin induced thrombocytopenia 

1. Monitoring patients for the development of HIT should be by performing serial 

platelet counts. Patients who have previously received UFH or LMWH within 100 days 

or in whom the history of recent exposure to heparins is not clear should have a 

platelet count performed within 24 hours of receiving the first dose of treatment. 

2. All other patients for whom monitoring is indicated should have platelet counts 

performed every two to three days from day four to day14 of exposure. 

3. In patients with HIT, alternative anticoagulation should be provided irrespective of 

whether or not there is evidence of a new thrombotic event unless the risk of 

haemorrhage is deemed excessive.419,420 Two drugs, lepirudin421,422 and 

danaparoid,419 are currently licensed in the UK for immediate management of this 

condition. 

Society of Obstetricians and Gynaecologists of Canada 

Diagnosis, evaluation and management of the hypertensive disorders of pregnancy 2008 

The third stage of labour should be actively managed with oxytocin 5 units IV or 10 units 

IM, particularly in the presence of thrombocytopenia or coagulopathy. (I-A) 

Society of Obstetric Medicine od Australia and New Zealand 

Guidelines for the management of hypertensive disorders of pregnancy 2008 

1. When relatively contraindicated (e.g. severe thrombocytopenia, coagulopathy or 

sepsis), fentanyl or remifentanil patient-controlled intravenous analgesia is preferred. 

2. … there are concerns with central neuraxial anaesthetic and analgesic techniques at 

higher levels (50-75 x 109 /L), and surgical bleeding may be increased even with 

moderate thrombocytopenia… 

Evidence-based reviews 

American College of Obstetricians and Gynecologists 

Medical management of ectopic pregnancy 2011 

Absolute Contraindications to Methotrexate Therapy - Preexisting blood dyscrasias, such 

as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia 

BJOG: An International Journal of Obstetrics & Gynaecology 

Screening in pregnancy for fetal or alloimmune thrombocytopenia: systematic review 

2010 

Screening for HPA-1a alloimmunisation detects about two cases in 1000 pregnancies. The 

calculated risk for perinatal ICH of 10% in pregnancies with severe FNAIT is an 

underestimation because studies without interventions were lacking. Screening of all 

pregnancies together with effective antenatal treatment such as intravenous 

3

immunoglobulin may reduce the mortality and morbidity associated with FNAIT. 

Clinical Knowledge Summaries 

Antiplatelet treatment 2009 

1. What are the adverse effects of dipyridamole? - Thrombocytopenia (isolated case 

reports). 

2. Do not prescribe aspirin - People with haemophilia or another haemorrhagic disorder 

(including thrombocytopenia). 

Cochrane Database of Systematic Reviews 

Antenatal interventions for fetomaternal alloimmune thrombocytopenia 2011 

The optimal management of fetomaternal alloimmune thrombocytopenia remains 

unclear. Lack of complete data sets for two trials and differences in interventions 

precluded the pooling of data from these trials which may have enabled a more 

developed analysis of the trial findings. Further trials would be required to determine 

optimal treatment (the specific medication and its dose and schedule). Such studies 

should include long-term follow up of all children and mothers. 

Medical treatments for idiopathic thrombocytopenic purpura during pregnancy 2009 

Current evidence indicates that compared to no medication, betamethasone did not 

reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during 

pregnancy. There is insufficient evidence to support the use of betamethasone for 

treating ITP. This Cohrane review does not provide evidence about other medical 

treatments for ITP during pregnancy. This systematic review also identifies the need for 

well-designed, adequately powered randomised clinical trials for this medical condition 

during pregnancy. Unless randomised clinical trials provide evidence of a treatment effect 

and the trade off between potential benefits and harms are established, policy-makers, 

clinicians, and academics should not use betamethasone for ITP in pregnant women. Any 

future trials on medical treatments for treating ITP during pregnancy should test a variety 

of important maternal, neonatal or both outcome measures, including maternal death, 

perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage. 

Health Technology Assessment Database 

The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for 

Gaucher’s 2007 

1. Anaemia, thrombocytopenia and leucopenia are common presenting features of type 

I Gaucher’s disease. 

2. The results of this RCT support the conclusion that ERT delivers beneficial effects for 

anaemia, thrombocytopenia and hepatomegaly, but that inducing changes in bone 

marrow may in fact exacerbate the development of osteopenia at certain sites in 

splenectomised adults. 

NHS Economic Evaluation Database 

Cost-effectiveness of antenatal screening for neonatal alloimmune thrombocytopenia 

2007 

The antenatal screening programme for neonatal alloimmune thrombocytopenia (NAIT) 

was found to be cost-effective in comparison with no screening. However, the net costs 

and benefits of the three strategies were fairly similar, and the study did not give clear 

guidance as to which one would be preferable. 

Prospective epidemiologic study of the outcome and cost-effectiveness of antenatal 

4

screening to detect neonatal alloimmune thrombocytopenia due to anti-HPA-1a 2006 

The effectiveness analysis showed that antenatal screening was more effective in 

detecting NAIT cases than no screening. 

NHS Evidence 

Antenatal interventions for fetomaternal alloimmune thrombocytopenia 2011 

Evidence shows that the harms of treating fetomaternal alloimmune thrombocytopenia 

with dexamethasone alone, or in combination with intravenous immunoglobulin may 

outweigh the benefits. 

Reducing or stopping antenatal administration of dexamethasone in fetomaternal 

alloimmune thrombocytopenia is likely to improve the quality of patient care and result 

in productivity savings by avoiding an unproven intervention with an unknown safety 

profile. 

UK Clinical Trials Gateway 

Interventional Study in Adult Subjects With Immune Thrombocytopenia Purpura Receiving 

Romiplostim 2010 

The purpose of this study is to describe the number of months with a subject platelet 

response over a 12 month treatment period and to describe ITP Remission Rates in Adult 

Subjects with Immune Thrombocytopenia Purpura Receiving Romiplostim 

UK National Screening Committee 

Thrombocytopenia 2006 

Screening for this condition should not be offered. This policy was reviewed in Jul 2006 

but no significant changes were made. It is due to be considered again in 2010/11, or 

earlier if significant new evidence emerges. 

Published research 

CINAHL results 

66. Thrombocytopenia in pregnancy: making the differential diagnosis. 

Author(s): Berkley EMF, Kilpatrick SJ 

Citation: Contemporary OB/GYN, 01 January 2009, vol./is. 54/1(36-41), 00903159 

Publication Date: 01 January 2009 

Abstract: When the platelet count drops, separating benign from life-threatening causes 

can prove quite challenging. Two experts explain the differences between gestational 

thrombocytopenia, heparin-induced thrombocytopenia, disseminated intravascular 

coagulopathy, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic 

purpura, and other disorders. 

Source: CINAHL 

Full Text: 

Available in fulltext at EBSCO Host 

67. Epidemiology, pathophysiology, and initial management of chronic immune 

thrombocytopenic purpura. 

5

Author(s): Pruemer J 

Citation: American Journal of Health-System Pharmacy, 03 January 2009, vol./is. 66/2(0-), 

10792082 


Abstract: Purpose. The incidence and epidemiology, the pathogenesis, the clinical 

symptoms and diagnosis and the first-line therapies for the management of chronic 

immune thrombocytopenic purpura (ITP) are discussed. In addition, the recommendations 

of two expert panels for the management of ITP are summarized.Summary. The diagnosis 

and management of chronic ITP are a challenge to the clinician caring for patients with 

this disease. Because the pathophysiology of ITP is not completely understood, a variety 

of medical interventions have been utilized in the management of ITP. National guidelines 

have established that oral corticosteroids are considered to be first-line therapy for 

chronic ITP. In addition, the use of intravenous immune globulin has demonstrated 

efficacy in the treatment of the disease. Intravenous methylprednisolone, anti-D 

immunoglobulin, and splenectomy have been utilized in recurrent or refractory cases. The 

use of other immunosuppressant medications and newer thrombopoietin stimulating 

agents may offer additional treatment options, as presented in the subsequent 

article.Conclusion. The initial management of chronic ITP should consist of the use of oral 

corticosteroids according to national guidelines. In the absence of a response to this firstline 

therapy, intravenous gamma globulin, intravenous methylprednisolone, anti-D 

immunoglobulin, or splenectomy may be considered. These treatments may also be 

utilized to manage recurrent cases of ITP, prior to consideration of second-line therapies. 


Full Text: 



68. Maternal thrombocytopenia-absent radius syndrome complicated by severe preeclampsia. 

Author(s): Wax JR, Crabtree C, Blackstone J, Pinette MG, Cartin A 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, 01 February 2009, vol./is. 

22/2(175-177), 14767058 

Publication Date: 01 February 2009 


Full Text: 


69. The diagnostic dilemma of thrombotic thrombocytopenic purpura/hemolytic 

uremic syndrome in the obstetric triage and emergency department: lessons from 4 

tertiary hospitals. 

Author(s): Stella CL, Dacus J, Guzman E, Dhillon P, Coppage K, How H, Sibai B 

Citation: American Journal of Obstetrics & Gynecology, 01 April 2009, vol./is. 200/4(0-), 

00029378 

Publication Date: 01 April 2009 

Abstract: OBJECTIVE: We report a series of occurrences of thrombotic thrombocytopenic 

purpura (TTP)/hemolytic uremic syndrome (HUS) in pregnancy that emphasizes early 

6

diagnosis. STUDY DESIGN: Fourteen pregnancies with TTP (n = 12) or HUS (n = 2) were 

studied. Analysis focused on clinical and laboratory findings on examination, initial 

diagnosis, and treatment. RESULTS: There were 14 pregnancies in 12 patients; 2 cases of 

TTP were diagnosed as recurrent. Five women were admitted to the emergency 

department (ED), and 7 patients were admitted to an obstetrics triage. Patients who were 

evaluated by an obstetrician were treated initially for hemolysis, elevated liver enzymes 

and low platelets syndrome/preeclampsia, whereas patients who were seen in the ED had 

a diagnosis that is commonplace in the ED (panic attack, domestic violence, 

gastroenteritis). Latency from the onset of symptoms to diagnosis ranged from 1-7 days. 

Plasmapheresis treatments in early gestation resulted in favorable maternal-neonatal 

outcome. Maternal and perinatal mortality rates were 25% each. CONCLUSION: TTP/HUS 

is a challenging diagnosis in obstetric triage and ED areas. We propose a management 

scheme that suggests how to triage patients for early diagnosis in pregnancy. 


70. Regional anesthesia in the parturient with idiopathic thrombocytopenia purpura. 

Author(s): Shaw MB 

Citation: International Student Journal of Nurse Anesthesia, 01 August 2009, vol./is. 

8/2(46-49), 

Publication Date: 01 August 2009 


71. Prenatal treatment of fetomaternal thrombocytopenia. 

Author(s): Vatopoulou T, Sorinola O 

Citation: British Journal of Hospital Medicine (17508460), 01 November 2009, vol./is. 

70/11(660-661), 17508460 

Publication Date: 01 November 2009 


Full Text: 


Available in print at Lincoln County Hospital Professional Library 

72. Is it time to implement HPA-1 screening in pregnancy? 

Author(s): Husebekk A, Killie MK, Kjeldsen-Kragh J, Skogen B 

Citation: Current Opinion in Hematology, 01 November 2009, vol./is. 16/6(497-502), 

10656251 


Abstract: PURPOSE OF REVIEW: The purpose of the review is to argue for and against 

introduction of HPA-1 typing of all pregnant women to reduce morbidity and mortality 

caused by foetal/neonatal alloimmune thrombocytopenia (FNAIT). RECENT FINDING: 

Several groups have done HPA-1 typing in cohorts of pregnant women. Results from a 

Norwegian study (>100,000 pregnancies) indicate that screening combined with simple 

intervention decreases morbidity and mortality due to FNAIT and is cost effective in 

Norway. Results from this study and several other studies show that there is correlation 

between the level of anti-HPA-1a antibodies in the mother and the severity of 

thrombocytopenia in the newborn. An important finding is that about 75% of women with 

antibodies are immunized in connection with delivery. Only 25% of the women are 

7

immunized during pregnancy. SUMMARY: Screening for FNAIT does not fully meet the 

criteria presented by the WHO. Nevertheless, the results of the Norwegian study strongly 

indicate that morbidity and mortality related to FNAIT can be reduced. If the recent 

attempts to make a vaccine aimed at prevention of immunization and/or tolerizing 

peptides or neutralizing antibodies for already immunized women are shown to be 

successful, screening must be implemented. 


73. Perinatal outcomes and complications of pregnancy in women with immune 


Author(s): Belkin A, Levy A, Sheiner E 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, 01 November 2009, vol./is. 

22/11(1081-1085), 14767058 



Full Text: 


74. Medical treatments for idiopathic thrombocytopenic purpura during pregnancy. 

Author(s): Martí-Carvajal AJ, Peña-Martí GE, Comunián-Carrasco G 

Citation: Cochrane Database of Systematic Reviews, 01 December 2009, vol./is. /4(0-), 

1469493X 

Publication Date: 01 December 2009 

Abstract: Background: 


Full Text: 

Available in fulltext at Wiley 

75. Immune thrombocytopenia in pregnancy. 

Author(s): Stavrou E, McCrae KR 

Citation: Hematology/Oncology Clinics of North America, 01 December 2009, vol./is. 

23/6(1299-1316), 08898588 


Abstract: Management of immune thrombocytopenia in pregnancy can be a complex and 

challenging task and may be complicated by fetal-neonatal thrombocytopenia. Although 

fetal intracranial hemorrhage is a rare complication of immune thrombocytopenia in 

pregnancy, invasive studies designed to determine the fetal platelet count before delivery 

are associated with greater risk than that of fetal intracranial hemorrhage and are 

discouraged. Moreover, the risk of neonatal bleeding complications does not correlate 

with the mode of delivery, and cesarean section should be reserved only for obstetric 

indications. 


76. Neonatal outcomes of pregnancy complicated by idiopathic thrombocytopenic 

purpura. 

8

Author(s): Ozkan H, Cetinkaya M, Koksal N, Ali R, Gunes AM, Baytan B, Ozkalemkas F, 

Ozkocaman V, Ozcelik T, Gunay U, Tunali A, Kimya Y, Cengiz C 

Citation: Journal of Perinatology, 01 January 2010, vol./is. 30/1(38-44), 07438346 


Abstract: Objective:The aim of this study was to determine the factors associated with the 

prognosis of newborns born to mothers with idiopathic thrombocytopenic purpura (ITP), 

and to compare the infants with/without thrombocytopenia in terms of maternal and 

neonatal characteristics.Study Design:We reviewed the charts of 29 parturients with ITP 

and their newborns who were born between January 1998 and December 2008.Result:A 

total of 16 (55%) gravidas had been diagnosed with ITP before pregnancy and 13 (45%) 

were diagnosed during pregnancy. Thrombocytopenia was observed in 21 gravidas. In 

total, 17 (58%) gravidas received treatment to increase the platelet count. The majority of 

deliveries (72.5%) were vaginal. The infant platelet counts at birth ranged from 20 to 336 x 

10 9 per liter. None of the neonates had complications attributable to the mode of 

delivery. Normal platelet counts were determined in 15 newborns, whereas 14 infants had 

thrombocytopenia at birth. Three (10.3%) neonates had mild, four neonates (13.7%) had 

moderate and seven neonates (24.1%) had severe thrombocytopenia. The age of the 

mothers having infants with thrombocytopenia was significantly higher (30-5.3 vs 25.3-3.8 

years), most of the infants (10/14 (71%)) were males (P

78. The use of angiogenic biomarkers to differentiate non-HELLP related 

thrombocytopenia from HELLP syndrome. 

Author(s): Young B, Levine RJ, Salahuddin S, Qian C, Lim KH, Karumanchi SA, Rana S 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, 01 May 2010, vol./is. 23/5(366- 

370), 14767058 

Publication Date: 01 May 2010 


Full Text: 


79. Neonatal alloimmune thrombocytopenia caused by an antibody specific for a 

newly identified allele of human platelet antigen-7. 

Author(s): Koh Y, Taniue A, Ishii H, Matsuyama N, Amakishi E, Hayashi T, Furuta RA, 

Fukumori Y, Hirayama F, Yoshimura K, Nagamine T, Tamai S, Nakano S 

Citation: Transfusion, 01 June 2010, vol./is. 50/6(1276-1284), 00411132 

Publication Date: 01 June 2010 


Full Text: 


Available in fulltext at the ULHT Library and Knowledge Services' eJournal collection ; 

Note: Click Athens Log In to access this journal. Enter NHS Athens username and password 

if required. 

80. Intracranial hemorrhage in alloimmune thrombocytopenia: stratified 

management to prevent recurrence in the subsequent affected fetus. 

Author(s): Bussel JB, Berkowitz RL, Hung C, Kolb EA, Wissert M, Primiani A, Tsaur FW, 

Macfarland JG 

Citation: American Journal of Obstetrics & Gynecology, 01 August 2010, vol./is. 203/2(0-), 

00029378 

Publication Date: 01 August 2010 

Abstract: OBJECTIVE: We sought to prevent intracranial hemorrhage (ICH) through 

antenatal management of alloimmune thrombocytopenia. STUDY DESIGN: A total of 33 

women (37 pregnancies) with alloimmune thrombocytopenia and ICH in a previous child 

were stratified according to the timing of the previous child's ICH: extremely high risk (HR) 

(n = 8) had ICH

81. Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: 

systematic review. 

Author(s): Kamphuis MM, Paridaans N, Porcelijn L, De Haas M, Van Der Schoot CE, Brand 

A, Bonsel GJ, Oepkes D 

Citation: BJOG: An International Journal of Obstetrics & Gynaecology, 01 October 2010, 

vol./is. 117/11(1335-1343), 14700328 

Publication Date: 01 October 2010 


Full Text: 




if required 

82. Bilateral retinal detachments and preeclampsia: thrombotic thrombocytopenic 

purpura or syndrome of haemolysis, elevated liver enzymes, low platelets? 

Author(s): Mendez-Figueroa H, Davidson C 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, 01 October 2010, vol./is. 

23/10(1268-1270), 14767058 

Publication Date: 01 October 2010 


Full Text: 


83. Clinical study on five cases of thrombotic thrombocytopenic purpura complicating 

pregnancy. 

Author(s): He Y, Chen Y, Zhao Y, Zhang Y, Yang W 

Citation: Australian & New Zealand Journal of Obstetrics & Gynaecology, 01 December 

2010, vol./is. 50/6(519-522), 00048666 



84. Established venous thromboembolism therapies: heparin, low molecular weight 

heparins, and vitamin k antagonists, with a discussion of heparin-induced 

thrombocytopenia. 

Author(s): Pendleton RC, Rodgers GM, Hull RD 

Citation: Clinics in Chest Medicine, 01 December 2010, vol./is. 31/4(691-706), 02725231 


Abstract: For a majority of patients with venous thromboembolism (VTE), initial treatment 

is straightforward and necessitates the immediate initiation of a parenteral anticoagulant 

(eg, heparin or low molecular weight heparin), simultaneous initiation of long-term 

therapy (eg, vitamin K antagonist), and discontinuation of the parenteral anticoagulant 

after 5 days assuming that the vitamin K antagonist is therapeutic. This standardized 

approach is based on numerous pivotal clinical trials completed over the past 3 decades. 

11

Yet, advances in standardized VTE treatment continue to evolve and include issues related 

to the selection and dosing of parenteral anticoagulants (eg, relative efficacy and dosing in 

the obese patient, patients with renal impairment, and pregnant patients), optimal 

location of initial care delivery, use of dosing initiation nomograms for vitamin K 

antagonists with the potential of gene-based dosing, and demonstration that longterm 

low molecular weight heparin therapy may be optimal for some patient populations (eg, 

those with active cancer). Further, in parallel with the evolution of VTE treatment, there 

have been remarkable advances in our understanding of heparin-induced 

thrombocytopenia, a prothrombotic complication of parenteral anticoagulant use. 


85. Reversal of thrombocytopenia in a pregnant woman after changing 

hemodiafiltration membranes... Am J Kidney Dis. 2010 Jun;55(6):e25-8. 

Author(s): Venditto M, Bourry E, Szumilak D, Deray G 

Citation: American Journal of Kidney Diseases, 01 March 2011, vol./is. 57/3(521-521), 

02726386 

Publication Date: 01 March 2011 


86. Immune thrombocytopenic purpura in pregnancy: a reappraisal of obstetric 

management and outcome. 

Author(s): Gasim, Turki 

Citation: Journal of Reproductive Medicine, 01 March 2011, vol./is. 56/3-4(163-168), 

00247758 


Abstract: OBJECTIVE: To evaluate the complications of pregnancy and perinatal outcome 

in women with idiopathic thrombocytopenic purpura (ITP). Study design: A retrospective 

analysis of 38 singleton pregnancies, their course, obstetric management and perinatal 

outcome of 32 patients with known ITP was undertaken. RESULTS: No major antenatal 

complications were noted among the patients. There were no maternal deaths, and only 1 

stillbirth occurred in the series. Fourteen infants were delivered by cesarean section and 

24 by vaginal delivery. Neonatal cord blood platelet count was performed in each of the 

live-born infants and revealed thrombocytopenia in 16 infants, but in only 6 (16.2%) of 

them was the cord blood platelet count


Abstract: BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is extremely rare. 

This disease and its prompt diagnosis are important because TTP in pregnancy carries a 

90% mortality rate. CASE: A 21-year-old woman underwent suction dilation and curettage 

for molar pregnancy. Postoperatively the patient developed severe hypertension, 

microangiopathic anemia, thrombocytopenia and chest pain associated with ischemic 

cardiac changes. Despite blood and plasma transfusions and steroid therapy, the patient 

continued to have worsening hemolysis and thrombocytopenia. TTP was diagnosed, and 

plasmapheresis led to a rapid recovery. CONCLUSION: TTP can occur with molar 

pregnancy. Making this diagnosis in a timely manner is crucial to ensure that potentially 

life-saving plasmapheresis is initiated in a timely manner. To our knowledge, this is the 

first reported case of thrombotic thrombocytopenic purpura with molar pregnancy. 


88. Thrombocytopenia in pregnancy. 

Author(s): Bockenstedt PL 

Citation: Hematology/Oncology Clinics of North America, 01 April 2011, vol./is. 25/2(293- 

310), 08898588 


Abstract: Thrombocytopenia in pregnancy is most frequently a benign process that does 

not require intervention. However, 35% of cases of thrombocytopenia in pregnancy are 

related to disease processes that may have serious bleeding consequences at delivery or 

for which thrombocytopenia may be an indicator of a more severe systemic disorder 

requiring emergent maternal and fetal care. Thus, all pregnant women with platelet 

counts less than 100,000/[mu]L require careful hematological and obstetric consultation 

to exclude more serious disorders. 


89. Microangiopathic disorders in pregnancy. 

Author(s): Pels SG, Paidas MJ 


322), 08898588 


Abstract: Microangiopathic disorders present with thrombocytopenia, hemolytic anemia, 

and multiorgan damage. In pregnancy, these disorders present a challenge both 

diagnostically and therapeutically, with widely overlapping clinical scenarios and disparate 

treatments. Although rare, a clear understanding of these diseases is important because 

devastating maternal and fetal outcomes may ensue if there is misdiagnosis and improper 

treatment. Microangiopathic disorders presenting in pregnancy are thus best assessed 

and treated by both obstetric and hematology teams. As a better understanding of the 

pathophysiology underlying each of the disease processes is gained, new diagnostic 

testing and therapies will be available, which will lead to improved outcomes. 


90. Transfusion medicine and the pregnant patient. 

Author(s): Lee AI, Kaufman RM 


13

413), 08898588 


Abstract: Alloimmunity in pregnancy is the basis for two of the major complications of 

pregnancy in transfusion medicine: hemolytic disease of the fetus and newborn (HDFN), 

and fetal and neonatal alloimmune thrombocytopenia (FNAIT). Use of Rh(D) immune 

globulin has dramatically reduced the incidence of HDFN in Rh(D)-mismatched 

pregnancies. Treatment of HDFN may involve intrauterine transfusion, with fetal and 

neonatal survival rates of 70% to 90%. Treatments for FNAIT include immune globulin, 

steroids, or in severe cases, intrauterine platelet transfusions. Transfusion medicine is 

central to the management of pregnancy-associated complications such as postpartum 

hemorrhage, parvovirus B19 infection, hemoglobinopathies, and aplastic anemia. 


91. Fetal alloimmune thrombocytopenia: is less invasive antenatal management safe? 

Author(s): Mechoulan A, Kaplan C, Muller JY, Branger B, Philippe HJ, Oury JF, Ville Y, Winer 

N 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, 01 April 2011, vol./is. 24/4(564- 

567), 14767058 



92. Antenatal interventions for fetomaternal alloimmune thrombocytopenia. 

Author(s): Rayment R, Brunskill SJ, Soothill PW, Roberts DJ, Bussel JB, Murphy MF 

Citation: Cochrane Database of Systematic Reviews, 01 May 2011, vol./is. /5(0-), 

1469493X 

Publication Date: 01 May 2011 

Abstract: Background: 


Full Text: 


MEDLINE Results 

1. [Thrombocytopenia in pregnancy and neonatal outcomes]. 

Author(s): Chao S, Zeng CM, Liu J 

Citation: Zhongguo Dangdai Erke Zazhi, October 2011, vol./is. 13/10(790-3), 1008- 

8830;1008-8830 (2011 Oct) 

Publication Date: October 2011 

Abstract: OBJECTIVE: To study the relationship between thrombocytopenia in pregnancy 

associated with various causes and neonatal outcomes.METHODS: Medical records of 140 

pregnant women with thrombocytopenia in pregnancy and the neonatal outcomes from 

January 2009 to December 2010 were reviewed retrospectively. The pregnant women 

were classified into four groups according to the causes of thrombocytopenia: gestational 

thrombocytopenia (GT; n=94), pregnancy with immune thrombocytopenic purpura (ITP; 

n=30), pregnancy with other hematological disease (aplastic anemia or myelodysplastic 

14

syndrome; n=12), and other causes (n=4): pregnancy induced hypertension syndrome, 

pregnancy with systemic lupus erythematosus, and pregnancy with alcoholic cirrhosis. The 

neonatal outcomes in the four groups were compared.RESULTS: The premature birth 

rates in the GT and the ITP groups were 11.3% and 16.7%, respectively. There was no 

significant difference between the two groups. The premature birth rate in the other 

hematological disease group was 53.8%, which was significantly higher than that in the GT 

(P

4971;1528-0020 (2011 Sep 1) 

Publication Date: September 2011 

Source: MEDLINE 

5. A new platelet alloantigen, Swi(a) , located on glycoprotein Ia identified in a family 

with fetal and neonatal alloimmune thrombocytopenia. 

Author(s): Kroll H, Feldmann K, Zwingel C, Hoch J, Bald R, Bein G, Bayat B, Santoso S 

Citation: Transfusion, August 2011, vol./is. 51/8(1745-54), 0041-1132;1537-2995 (2011 

Aug) 

Publication Date: August 2011 

Abstract: BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a 

bleeding disorder caused by transplacental passage of maternal antibodies to fetuses 

whose platelets (PLTs) express the corresponding human PLT antigen (HPA). STUDY 

DESIGNS AND METHODS: We observed a fetus with FNAIT who died from a severe 

intracranial hemorrhage. Analysis of maternal serum in antigen capture assay with 

paternal PLTs showed reactivity with PLT glycoprotein (GP)IIb/IIIa (alpha(IIb) beta(3) ) and 

GPIa/IIa (alpha(2) beta(1) integrin), indicating the presence of anti-HPA-1a and an 

additional alloantibody against GPIa (termed anti-Swi(a) ).RESULTS: By immunochemical 

studies, the localization of the Swi(a) antigen on GPIa/IIa could be confirmed. Analysis of 

paternal GPIa full-length cDNA showed a single-nucleotide substitution C(3347) T in Exon 

28 resulting in a Thr(1087) Met amino acid substitution. Testing of family members by 

polymerase chain reaction-restriction fragment length polymorphism using MslI 

endonuclease showed perfect correlation with phenotyping. Extended family and 

population studies showed that 4 of 10 members of the paternal family but none of 500 

unrelated blood donors were Swi(a) carriers. Expression studies on allele-specific 

transfected Chinese hamster ovary (CHO) cells confirmed that the single-amino-acid 

substitution Thr(1087) Met was responsible for the formation of the Swi(a) epitope. 

Adhesion of CHO cells expressing the Swi(a) alloantigen to immobilized collagens was not 

impaired compared to the wild-type control and was not inhibited by anti-Swi(a) 

alloantibodies.CONCLUSION: In this study we defined a new PLT alloantigen Swi(a) that 

was involved in a case of additional immunization against HPA-1a. Our observations 

demonstrate that combinations of PLT-specific alloantibodies may comprise lowfrequency 

alloantigens. Copyright 2011 American Association of Blood Banks. 


Full Text: 

Available in fulltext at the ULHT Library and Knowledge Services' eJournal collection ; Note: 

Click Athens Log In to access this journal. Enter NHS Athens username and password if 

required. 

6. Fetal and neonatal alloimmune thrombocytopenia: prenatal interventions. 

Author(s): Kamphuis MM, Oepkes D 

Citation: Prenatal Diagnosis, July 2011, vol./is. 31/7(712-9), 0197-3851;1097-0223 (2011 

Jul) 

Publication Date: July 2011 

Abstract: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially 

devastating condition, which may lead to intracranial haemorrhage (ICH) in the fetus or 

neonate, often with death or major neurological damage as consequence. In the absence 

of screening, preventive measures are only possible in the next pregnancy of women with 

16

an affected child. Controversy exists on the best intervention to minimise the risk of ICH. 

Most centres have abandoned treatment with serial fetal blood sampling (FBS) and 

platelet transfusions, because of a high rate of complications and the availability of quite 

effective non-invasive alternatives. In pregnancies with FNAIT and a previous affected 

child without ICH, weekly intravenous administration of immunoglobulins to the mother 

appears close to 100% effective to prevent fetal or neonatal ICH. Some centres add 

prednisone; this combination leads to slightly higher platelet counts at birth. In pregnant 

women with a previous child with ICH, the recurrence risk seems particularly high, and 

more aggressive maternal medical treatment is recommended, starting earlier with 

immunoglobulins. Whether a higher intravenous immunoglobulin dose or the addition of 

prednisone is really necessary is unclear. What does seem to be clear is that the use of FBS 

should be minimised, possibly even abandoned completely. Copyright Copyright 2011 

John Wiley & Sons, Ltd. 


7. Exacerbation of thrombocytopenia in a pregnant woman with thrombocytopeniaabsent 

radius syndrome. 

Author(s): Bot-Robin V, Vaast P, Deruelle P 

Citation: International Journal of Gynaecology & Obstetrics, July 2011, vol./is. 114/1(77-8), 

0020-7292;1879-3479 (2011 Jul) 



8. Successful management of a planned pregnancy in severe congenital thrombotic 

thrombocytopaenic purpura: the Upshaw-Schulman syndrome. 

Author(s): Richter J, Strandberg K, Lindblom A, Strevens H, Karpman D, Wide-Swensson D 

Citation: Transfusion Medicine, June 2011, vol./is. 21/3(211-3), 0958-7578;1365-3148 

(2011 Jun) 

Publication Date: June 2011 


9. A founder mutation in the MPL gene causes congenital amegakaryocytic 

thrombocytopenia (CAMT) in the Ashkenazi Jewish population. 

Author(s): Jalas C, Anderson SL, Laufer T, Martimucci K, Bulanov A, Xie X, Ekstein J, Rubin 

BY 

Citation: Blood Cells Molecules & Diseases, June 2011, vol./is. 47/1(79-83), 1079- 

9796;1096-0961 (2011 Jun 15) 


Abstract: Congenital amegakaryocytic thrombocytopenia (MIM #604498) (CAMT) is a rare 

inherited disease presenting as severe thrombocytopenia in infancy. Untreated, many 

CAMT patients develop aplastic anemia within the first decade of life; the only effective 

treatment of CAMT is bone marrow transplantation. CAMT is the result of the presence of 

homozygous or compound heterozygous mutations in the thrombopoietin receptorencoding 

gene, MPL. We report here the identification and characterization of a founder 

mutation in MPL in the Ashkenazi Jewish (AJ) population. This mutation, termed 

c.79+2T>A, is a T to A transversion in the invariant second base of the intron 1 donor 

splice site. Analysis of a random sample of 2018 individuals of AJ descent revealed a 

carrier frequency of approximately 1 in 75. Genotyping of six loci adjacent to the MPL 

17

gene in the proband and in the 27 individuals identified as carriers of the c.79+2T>A 

mutation revealed that the presence of this mutation in the AJ population is due to a 

single founder. The observed carrier frequency predicts an incidence of CAMT in the AJ 

population of approximately 1 in 22,500 pregnancies. The identification of this mutation 

will enable population carrier testing and will facilitate the identification and treatment of 

individuals homozygous for this mutation. Copyright Copyright 2011 Elsevier Inc. All rights 

reserved. 


10. Fetomaternal alloimmune thrombocytopenia: increasing awareness. 

Author(s): Dickinson JE 

Citation: Australian & New Zealand Journal of Obstetrics & Gynaecology, June 2011, 

vol./is. 51/3(189-90), 0004-8666;1479-828X (2011 Jun) 



11. Management of severe immune thrombocytopenic purpura in a pregnant woman 

with inevitable preterm forceps breech delivery. 

Author(s): Cho FN 

Citation: Taiwanese Journal of Obstetrics & Gynecology, June 2011, vol./is. 50/2(227-9), 

1028-4559;1875-6263 (2011 Jun) 



12. [Advance of clinical study on immune thrombocytopenia caused by irregular 

antibodies]. 

Author(s): Zhu LL, Zhang CG 

Citation: Zhongguo Shi Yan Xue Ye Xue Za Zhi, June 2011, vol./is. 19/3(839-42), 1009- 

2137;1009-2137 (2011 Jun) 


Abstract: The platelet antibodies mainly include platelet-specific and related antibodies, 

which belong to irregular antibodices. They are produced by autoimmune, drug-induced 

or isoimmunization (such as pregnancy, blood transfusion and so on), the irregular IgG 

and/or IgM antibodies produce and lead to platelet transfusion refractoriness (PTR), posttransfusion 

purpura (PTP) and isoimmune neonatal throbocytopenic purpura (INTP), 

idiopathic thrombocytopenic purpura and so on. It is very necessary to screen and identify 

the irregular antibodies before blood transfusion or parturition. Except some serological 

detections should be done first, flow cytometry and molecular biological techniques such 

as PCR and PCR-SSP are applied to detect the difficult-matching patients' genotypes and 

fetal genotypes in order to further predict fetal INTP and to provide the right blood for 

difficult-matching patients, therefore, some measures must be taken early for prevention 

and treatment of immune thrombocytopenic purpura. In this review, the production, 

typing and laboratory tests of irregular antibodies, as well as the pathogenesis and clinical 

symptoms of diseases caused by irregular antibodies, and the current progress are 

summarized. 


13. Use of fondaparinux in a pregnant woman with pulmonary embolism and heparin- 

18

induced thrombocytopenia. 

Author(s): Ciurzynski M, Jankowski K, Pietrzak B, Mazanowska N, Rzewuska E, Kowalik R, 

Pruszczyk P 

Citation: Medical Science Monitor, May 2011, vol./is. 17/5(CS56-9), 1234-1010;1643-3750 

(2011 May) 

Publication Date: May 2011 

Abstract: BACKGROUND: A serious complication of heparin treatment, heparin-induced 

thrombocytopenia (HIT) is rarely observed in pregnant women. Drug therapy during 

pregnancy should always be chosen to minimize fetal risk. The management of HIT in 

pregnancy represents a medical challenge. Unlike heparins, the anticoagulants used in 

patients with HIT do cross the placenta, with unknown fetal effects.CASE REPORT: We 

present a case of a 24-year-old female presenting for care at 34 weeks of gestation with 

acute pulmonary embolism treated initially with unfractionated heparin (UFH) and low 

molecular weight heparin (LMWH), who developed HIT. She was then successfully treated 

with fondaparinux.CONCLUSIONS: To the best of our knowledge, this is one of the first 

case reports describing a successful use of fondaparinux in the treatment of HIT in a thirdtrimester 

pregnant woman, providing a novel approach for this subset of patients. 


14. Microangiopathic disorders in pregnancy. 

Author(s): Pels SG, Paidas MJ 

Citation: Hematology - Oncology Clinics of North America, April 2011, vol./is. 25/2(311-22, 

viii), 0889-8588;1558-1977 (2011 Apr) 

Publication Date: April 2011 

Abstract: Microangiopathic disorders present with thrombocytopenia, hemolytic anemia, 

and multiorgan damage. In pregnancy, these disorders present a challenge both 

diagnostically and therapeutically, with widely overlapping clinical scenarios and disparate 

treatments. Although rare, a clear understanding of these diseases is important because 

devastating maternal and fetal outcomes may ensue if there is misdiagnosis and improper 

treatment. Microangiopathic disorders presenting in pregnancy are thus best assessed 

and treated by both obstetric and hematology teams. As a better understanding of the 

pathophysiology underlying each of the disease processes is gained, new diagnostic 

testing and therapies will be available, which will lead to improved outcomes. Copyright 

Copyright 2011 Elsevier Inc. All rights reserved. 



Author(s): Bockenstedt PL 

Citation: Hematology - Oncology Clinics of North America, April 2011, vol./is. 25/2(293- 

310, vii-viii), 0889-8588;1558-1977 (2011 Apr) 







counts less than 100,000/muL require careful hematological and obstetric consultation to 

19

exclude more serious disorders. Copyright Copyright 2011 Elsevier Inc. All rights reserved. 


16. Fetal alloimmune thrombocytopenia: is less invasive antenatal management 

safe?. 

Author(s): Mechoulan A, Kaplan C, Muller JY, Branger B, Philippe HJ, Oury JF, Ville Y, Winer 

N, French GROG 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, April 2011, vol./is. 24/4(564-7), 

1476-4954;1476-4954 (2011 Apr) 


Abstract: OBJECTIVES: The aim of this study was to review recent multicenter data on 

antenatal management of anti-HPA-1a fetal alloimmune thrombocytopenia and, based on 

this retrospective study and on recent literature, to evaluate if FBS modified the 

obstetrical management.MATERIAL AND METHODS: This retrospective study in France 

includes 23 pregnancies in 21 women who had a previous thrombocytopenic infant due to 

anti HPA-1a alloimmunization. All pregnant women received intravenous immunoglobulin 

(IVIG) treatment, with or without corticosteroids. Fetal blood sampling (FBS) was 

performed before any therapy (four cases) or during pregnancy (nine cases).RESULTS: 

Infants whose mother received treatment had a significantly higher neonatal platelet 

count than the corresponding sibling (p = 0.003). In eight cases, therapy was started late 

during pregnancy. In three cases, treatment was discontinued 3 or 4 weeks before birth, 

and this was associated with a poorer result. No in utero intracranial hemorrhage was 

recorded in the infants for whom maternal therapy continued to term. Adverse effects 

were not observed in any case. All babies were delivered by cesarean even when FBS was 

performed. One emergency cesarean was performed for fetal bradycardia after 

FBS.CONCLUSION: This study confirmed that maternal therapy with intravenous 

immunoglobulin for fetal alloimmune thrombocytopenia gives satisfactory results. It also 

showed that a less invasive approach, especially a reduction in the number of fetal blood 

samples, is possible without deleterious consequences. This observation suggests also to 

start IVIG early during pregnancy and to continue treatment up to delivery. 


17. Life-threatening postpartum hemolysis, elevated liver functions tests, low 

platelets syndrome versus thrombocytopenic purpura - Therapeutic plasma exchange is 

the answer. 

Author(s): Nasa P, Dua JM, Kansal S, Chadha G, Chawla R, Manchanda M 

Citation: Indian Journal of Critical Care Medicine, April 2011, vol./is. 15/2(126-9), 0972- 

5229;1998-359X (2011 Apr) 


Abstract: The differential diagnosis of life-threatening microangiopathic disorders in a 

postpartum female includes severe preeclampsia-eclampsia, hemolysis, elevated liver 

functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There 

is considerable overlapping in the clinical and laboratory findings between these 

conditions, and hence an exact diagnosis may not be always possible. However, there is 

considerable maternal mortality and morbidity associated with these disorders. This case 

underlines the complexity of pregnancy-related microangiopathies regarding their 

differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange 

in their management. 


20

Full Text: 

Available in fulltext at National Library of Medicine 


hemodiafiltration membranes. 

Author(s): Venditto M, Bourry E, Szumilak D, Deray G 

Citation: American Journal of Kidney Diseases, March 2011, vol./is. 57/3(521), 0272- 

6386;1523-6838 (2011 Mar) 

Publication Date: March 2011 


19. Prediction of the fetal status in noninvasive management of alloimmune 


Author(s): Bertrand G, Drame M, Martageix C, Kaplan C 

Citation: Blood, March 2011, vol./is. 117/11(3209-13), 0006-4971;1528-0020 (2011 Mar 

17) 


Abstract: Fetal/neonatal alloimmune thrombocytopenia is the most common cause of 

severe thrombocytopenia in the fetus and in an otherwise healthy newborn. To counter 

the consequences of severe fetal thrombocytopenia, antenatal therapies have been 

implemented. Predictive parameters for fetal severe thrombocytopenia are important for 

the development of noninvasive strategy and tailored intervention. We report here data 

concerning 239 pregnancies in 75 HPA-1bb women. Analysis of the index cases (diagnosis 

of fetal/neonatal alloimmune thrombocytopenia) did not show any significant correlation 

between the severity of the disease and the maternal genetic background (ABO blood 

group and HLA-DRB3 allele). Subsequent pregnancies were managed, and therapy 

effectiveness was evaluated. The highest mean newborn platelet count was observed for 

a combination of intravenous immunoglobulin and steroids (135 x 109/L; 54 newborns) 

compared with intravenous immunoglobulin alone (89 x 109/L; 27 newborns). The 

maternal anti-HPA-1a antibody concentration measured before any treatment and before 

28 weeks of gestation was predictive of the fetal status. The weighted areas under curves 

of the maternal alloantibody concentrations were predictive of therapy response. To 

conclude, this large retrospective survey gives new insights on maternal predictive 

parameters for fetal status and therapy effectiveness allowing noninvasive strategies. 


Full Text: 

Available in fulltext at Highwire Press 

20. Thrombotic thrombocytopenic purpura with complete molar pregnancy: a case 

report. 

Author(s): Meng H, Kumar NS, Nannapaneni J, Inglis SR 

Citation: Journal of Reproductive Medicine, March 2011, vol./is. 56/3-4(169-71), 0024- 

7758;0024-7758 (2011 Mar-Apr) 


Abstract: BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is extremely rare. 

This disease and its prompt diagnosis are important because TTP in pregnancy carries a 

90% mortality rate.CASE: A 21-year-old woman underwent suction dilation and curettage 

21

for molar pregnancy. Postoperatively the patient developed severe hypertension, 

microangiopathic anemia, thrombocytopenia and chest pain associated with ischemic 

cardiac changes. Despite blood and plasma transfusions and steroid therapy, the patient 

continued to have worsening hemolysis and thrombocytopenia. TTP was diagnosed, and 

plasmapheresis led to a rapid recovery.CONCLUSION: TTP can occur with molar 

pregnancy. Making this diagnosis in a timely manner is crucial to ensure that potentially 

life-saving plasmapheresis is initiated in a timely manner. To our knowledge, this is the 

first reported case of thrombotic thrombocytopenic purpura with molar pregnancy. 



management and outcome. 

Author(s): Gasim T 

Citation: Journal of Reproductive Medicine, March 2011, vol./is. 56/3-4(163-8), 0024- 

7758;0024-7758 (2011 Mar-Apr) 


Abstract: OBJECTIVE: To evaluate the complications of pregnancy and perinatal outcome 

in women with idiopathic thrombocytopenic purpura (ITP).STUDY DESIGN: A retrospective 

analysis of 38 singleton pregnancies, their course, obstetric management and perinatal 

outcome of 32 patients with known ITP was undertaken.RESULTS: No major antenatal 

complications were noted among the patients. There were no maternal deaths, and only 1 

stillbirth occurred in the series. Fourteen infants were delivered by cesarean section and 

24 by vaginal delivery. Neonatal cord blood platelet count was performed in each of the 

live-born infants and revealed thrombocytopenia in 16 infants, but in only 6 (16.2%) of 

them was the cord blood platelet count < 50 x 10(9)/L. There was no neonatal death in the 

study, although 6 infants required supportive treatment with corticosteroids and 

intravenous immunoglobulin G. No maternal features could be used to predict the 

neonatal platelet count at birth. These results are comparable with other studies in the 

recent literature.CONCLUSION: Due to the low incidence of poor neonatal outcome in 

mothers with ITP, obstetric intervention based solely on their platelet count is not 

justified. Every patient with ITP should be managed individually, and the routine use of 

cesarean section should be abandoned. 


22. TAR syndrome and esophagial atresia: a concomitant or variant condition?. 

Author(s): Peker E, Cagan E, Dogan M, Sal E, Kirimi E 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, February 2011, vol./is. 24/2(226- 

8), 1476-4954;1476-4954 (2011 Feb) 

Publication Date: February 2011 

Abstract: Thrombocytopenia with absent radii (TAR) is rare cause of neonatal 

thrombocytopenia. TAR syndrome and esophageal atresia with tracheoesophageal fistula 

has been reported in only two cases in literature. Our case was the first in literature with 

unilateral TAR syndrome and bilateral absence of thumbs accompanying EA. 


23. Fetal and neonatal alloimmune thrombocytopenia: harvesting the evidence to 

develop a clinical approach to management. 

Author(s): Symington A, Paes B 

22

Citation: American Journal of Perinatology, February 2011, vol./is. 28/2(137-44), 0735- 

1631;1098-8785 (2011 Feb) 


Abstract: Neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of 

severe thrombocytopenia in an otherwise healthy newborn. The most serious 

complication is intracranial hemorrhage, which can occur either in the fetus or the 

newborn. Despite the known serious sequelae, both antenatal management and neonatal 

treatment modalities are plagued by the lack of gold standard evidence to appropriately 

direct therapy. Maternal, risk-based therapeutic approaches range from invasive protocols 

to relatively benign noninvasive strategies to avoid serious procedural complications. 

Intravenous immunoglobulin (IVIG) with or without steroids and fetal blood sampling 

constitute the mainstay of antenatal management. Neonatal interventions principally 

focus on the use of antigen-negative compatible or random donor platelets and IVIG. 

While awaiting the results of controlled trials, each institution must develop a 

standardized, collaborative, multidisciplinary approach to the screening, diagnostic 

evaluation, and management of unexpected and anticipated NAIT based on experience, 

product availability, and emerging scientific data. Copyright Thieme Medical Publishers. 


24. The incidence and outcomes of fetomaternal alloimmune thrombocytopenia: a 

UK national study using three data sources. 

Author(s): Knight M, Pierce M, Allen D, Kurinczuk JJ, Spark P, Roberts DJ, Murphy MF 

Citation: British Journal of Haematology, February 2011, vol./is. 152/4(460-8), 0007- 

1048;1365-2141 (2011 Feb) 


Abstract: Fetomaternal alloimmune thrombocytopenia (FMAIT) is the most common 

cause of severe neonatal thrombocytopenia in otherwise well, term infants. First 

pregnancies are often severely affected. This descriptive, population-based national study 

was undertaken in order to inform the case for antenatal screening. Cases were identified 

using three sources and capture-recapture techniques used to generate a robust 

incidence estimate. One hundred and seventy three cases were identified between 

October 2006 and September 2008. An extra 20 cases were estimated from capturerecapture 

analysis, giving an estimated incidence of clinically detected FMAIT of 12.4 

cases per 100[em space]000 total births (95%confidence interval: 10.7, 14.3). Fifty-two 

cases (30%) were known at the start of pregnancy; 120 (70%) were unknown (n=115) or 

unrecognized (n=5). Unknown cases were more likely to experience a haemorrhagic 

complication (67% vs. 5%) (P

Abstract: BACKGROUND: Current guidelines recommend glucocorticoids and splenectomy 

as standard 1(st) and 2(nd) line treatments for chronic immune thrombocytopenia (ITP). 

We sought to find out how German ITP-patients are treated with respect to these 

guidelines.METHODS: Members of a patient support association >=18 years with a selfreported 

history of chronic ITP>12 months were surveyed with a web-based 

questionnaire.RESULTS: 122 questionnaires were evaluated. 70% of patients had chronic 

ITP for more than 5 years and 20% an average platelet count of

count at birth and preterm birth). Lack of complete data sets and important differences in 

interventions precluded the pooling of data from these trials.AUTHORS' CONCLUSIONS: 

The optimal management of fetomaternal alloimmune thrombocytopenia remains 

unclear. Lack of complete data sets for two trials and differences in interventions 

precluded the pooling of data from these trials which may have enabled a more 

developed analysis of the trial findings. Further trials would be required to determine 

optimal treatment (the specific medication and its dose and schedule). Such studies 

should include long-term follow up of all children and mothers. 


Full Text: 


27. Rituximab for management of refractory pregnancy-associated immune 


Author(s): Gall B, Yee A, Berry B, Birchman D, Hayashi A, Dansereau J, Hart J 

Citation: Journal of Obstetrics & Gynaecology Canada: JOGC, December 2010, vol./is. 

32/12(1167-71), 1701-2163;1701-2163 (2010 Dec) 

Publication Date: December 2010 

Abstract: BACKGROUND: Rituximab is a novel therapy for immune thrombocytopenic 

purpura (ITP); however, information about its safety in pregnancy is limited. This case 

illustrates the successful use of rituximab to treat pregnancy-associated ITP.CASE: A 34- 

year-old woman presented with severe ITP at 23 weeks' gestation. Standard treatment 

with corticosteroids, intravenous immune globulin, and splenectomy failed to raise the 

platelet count. Due to ongoing bleeding, rituximab was given in the 26th week of 

pregnancy. The platelet count rose to over 100 x 10(9)/L after four weeks. The neonatal B- 

lymphocyte count normalized at four months after delivery. There were no neonatal 

complications of rituximab therapy.CONCLUSION: Rituximab may be safe for use in 

treating pregnancy-associated ITP. This case highlights the need to investigate further the 

safety and efficacy of rituximab in pregnancy. 



pregnancy. 

Author(s): He Y, Chen Y, Zhao Y, Zhang Y, Yang W 

Citation: Australian & New Zealand Journal of Obstetrics & Gynaecology, December 2010, 

vol./is. 50/6(519-22), 0004-8666;1479-828X (2010 Dec) 


Abstract: OBJECTIVE: The aim of this study was to investigate the potential role of 

ADAMTS13 analysis in the early recognition and management of thrombotic 

thrombocytopenic purpura (TTP) in pregnant women.METHODS: Five cases of TTP were 

evaluated retrospectively. Clinical and laboratory findings, von Willebrand factor (vWF)- 

cleaving metalloprotease (ADAMTS13) activity and maternal and neonatal outcome were 

recorded and analysed.RESULTS: Five cases were all nulliparous. ADAMTS13 assay was 

performed and the enzyme activity was less than 5% of the normal controls in three cases. 

Gene mutation in the 9th exon resulting in amino acid exchange 349Arg->Cys in 

ADAMTS13 was identified in one patient. After treatment including transfusion of freshfrozen 

plasma (n = 5), packed red blood cells (n = 5), platelet transfusions (n = 2) and/or 

continued renal replacement therapy (CRRT) (n = 1) and plasma exchange (n = 2), three 

patients were alive, one died on postpartum day 6 in hospital without plasma exchange 

25

and one of familial TTP died three months after discharge.CONCLUSION: With increasing 

awareness, extra-attention must be paid to patients with thrombotic microangiopathy 

and to measurement of ADAMTS13 activity for early diagnosis. Although severe 

ADAMTS13 deficiency may be helpful for TTP, it may not be sensitive enough to identify 

all TTP patients. Therefore, despite ADAMTS13 result positive or negative, prompt 

aggressive management should include early termination of pregnancy, plasma 

transfusion and/or plasma exchange. Copyright 2010 The Authors. Australian and New 

Zealand Journal of Obstetrics and Gynaecology Copyright 2010 The Royal Australian and 

New Zealand College of Obstetricians and Gynaecologists. 


29. Established venous thromboembolism therapies: heparin, low molecular weight 

heparins, and vitamin K antagonists, with a discussion of heparin-induced 


Author(s): Pendleton RC, Rodgers GM, Hull RD 

Citation: Clinics in Chest Medicine, December 2010, vol./is. 31/4(691-706), 0272- 

5231;1557-8216 (2010 Dec) 
















thrombocytopenia, a prothrombotic complication of parenteral anticoagulant use. 

Copyright Copyright 2010 Elsevier Inc. All rights reserved. 


30. Fetal genotyping for platelets antigens: a precise tool for alloimmune 

thrombocytopenia: case report and literature review. 

Author(s): Nomura ML, Couto E, Martinelli BM, Barjas-Castro ML, Barini R, Passini Junior R, 

Castro V 

Citation: Archives of Gynecology & Obstetrics, November 2010, vol./is. 282/5(573-5), 

0932-0067;1432-0711 (2010 Nov) 

Publication Date: November 2010 

Abstract: INTRODUCTION: Maternal-fetal alloimmune thrombocytopenia complicates 

about 0.1% of all pregnancies and is associated with major fetal and neonatal morbidity 

and mortality, especially spontaneous central nervous system bleeding leading to death 

and neurological handicaps. Successful prevention and treatment depend on the 

identification of at-risk possible carriers of anti-platelet antibodies.CASE REPORT: We 

report a case of a mother with a previous child that developed neonatal hemorrhage; 

HPA-5b anti-platelet antibodies were detected post-natally. During the next pregnancy, 

26

fetal genotyping confirmed the presence of HPA-5b antigen; she was treated with weekly 

intravenous human immunoglobulin and oral prednisone. Pregnancy evolved without 

remarkable features and a full-term baby was delivered, with normal platelet 

counts.CONCLUSION: Fetal alloimmune thrombocytopenia is a potentially lethal condition, 

but early detection and prevention lead to successful outcome in most cases. 


Full Text: 


31. Antenatal treatment of fetal alloimmune thrombocytopenia: a current 

perspective. 

Author(s): Vinograd CA, Bussel JB 

Citation: Haematologica, November 2010, vol./is. 95/11(1807-11), 0390-6078;1592-8721 

(2010 Nov) 



Full Text: 



32. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin 

infusion. 

Author(s): Giers G, Wenzel F, Stockschlader M, Riethmacher R, Lorenz H, Tutschek B 

Citation: Haematologica, November 2010, vol./is. 95/11(1921-6), 0390-6078;1592-8721 

(2010 Nov) 


Abstract: BACKGROUND: Different therapeutic approaches have been used in fetalneonatal 

alloimmune thrombocytopenia, but many centers administer immunoglobulin G 

infusions to the pregnant woman. We studied the effect of maternal antenatal 

immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune 

thrombocytopenia.DESIGN AND METHODS: We retrospectively analyzed the clinical 

courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated 

with immunoglobulin G infusions in a single center between 1999 and 2005. In a centerspecific 

protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant 

women with previously affected neonates and four women with strong platelet 

antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each 

infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts 

and immunoglobulin G levels.RESULTS: There were 30 fetuses with fetal alloimmune 

thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts 

between 4x10(9)/L and 130x10(9)/L and antibody-coated fetal platelets using a 

glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G 

infusions fetal platelet counts did not change significantly. Maternal and fetal 

immunoglobulin G levels, measured before every infusion, increased significantly with the 

number of maternal immunoglobulin G infusions.CONCLUSIONS: In this group of fetuses 

with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was 

achieved as a result of regular maternal immunoglobulin G infusions. 


27

Full Text: 



33. Pulmonary embolectomy in heparin-induced thrombocytopenia and thrombosis? 

Safety of heparin use. 

Author(s): Sachithanandan A 

Citation: Interactive Cardiovascular & Thoracic Surgery, November 2010, vol./is. 

11/5(681), 1569-9285;1569-9285 (2010 Nov) 



Full Text: 


34. Successful surgical management of massive pulmonary embolism during the 

second trimester in a parturient with heparin-induced thrombocytopenia. 

Author(s): Hajj-Chahine J, Jayle C, Tomasi J, Corbi P 

Citation: Interactive Cardiovascular & Thoracic Surgery, November 2010, vol./is. 11/5(679- 

81), 1569-9285;1569-9285 (2010 Nov) 


Abstract: Cardiopulmonary bypass during pregnancy is associated with a high fetal and 

maternal mortality. We report a successful pulmonary embolectomy in a woman at the 

27th week of pregnancy; we performed surgical pulmonary embolectomy under 

cardiopulmonary bypass to restore adequate hemodynamic stability and to relieve right 

ventricle strain. We discuss the decision made for the preferred anticoagulation drug in 

the setting of heparin-induced thrombocytopenia in the gravida. The pregnancy was 

carried to term and she delivered a healthy boy at 38[NON-BREAKING SPACE]weeks of 

gestation. 


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35. Repeated intrauterine IgG infusions in foetal alloimmune thrombocytopenia do 

not increase foetal platelet counts. 

Author(s): Giers G, Wenzel F, Riethmacher R, Lorenz H, Tutschek B 

Citation: Vox Sanguinis, November 2010, vol./is. 99/4(348-53), 0042-9007;1423-0410 

(2010 Nov) 


Abstract: BACKGROUND AND OBJECTIVES: Foetal alloimmune thrombocytopenia (FNAIT) 

is often treated transplacentally with maternally administered i.v. immunoglobulins, but 

not all foetuses show a consistent platelet increase during such treatment.MATERIALS 

AND METHODS: We retrospectively analysed data from a cohort of ten foetuses with 

FNAIT treated by direct foetal immunoglobulin infusion. Foetal treatment was begun 

between 17 and 25 weeks and continued until 36 weeks with weekly cordocenteses and 

foetal immunoglobulin infusions.RESULTS: While foetal IgG levels increased steadily 

during weekly IgG infusions, foetal platelet counts remained unchanged.CONCLUSION: 

28

Our retrospective study presents a unique analysis of a historical cohort, contributing to 

the ongoing debate about the treatment of choice for foetal alloimmune 

thrombocytopenia. Copyright 2010 The Author(s). Vox Sanguinis Copyright 2010 

International Society of Blood Transfusion. 


Full Text: 


36. Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal 

Fc receptor in the pathogenesis and therapy. 

Author(s): Chen P, Li C, Lang S, Zhu G, Reheman A, Spring CM, Freedman J, Ni H 

Citation: Blood, November 2010, vol./is. 116/18(3660-8), 0006-4971;1528-0020 (2010 Nov 

4) 


Abstract: Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding 

disorder in which maternal antibodies cross the placenta and destroy fetal/neonatal 

platelets. It has been demonstrated that the neonatal Fc receptor (FcRn) regulates 

immunoglobulin G (IgG) homeostasis and plays an important role in transplacental IgG 

transport. However, the role of FcRn in the pathogenesis and therapy of FNIT has not 

been studied. Here, we developed an animal model of FNIT using combined beta3 

integrin-deficient and FcRn-deficient (beta3(-/-)FcRn(-/-)) mice. We found that beta3(-/- 

)FcRn(-/-) mice are immunoresponsive to beta3(+/+)FcRn(-/-) platelets. The generated 

antibodies were beta3 integrin specific and were maintained at levels that efficiently 

induced thrombocytopenia in adult beta3(+/+)FcRn(-/-) mice. FNIT was observed when 

immunized beta3(-/-)FcRn(+/+) females were bred with beta3(+/+)FcRn(+/+) males, while 

no FNIT occurred in beta3(-/-)FcRn(-/-) females bred with beta3(+/+)FcRn(-/-) males, 

suggesting that FcRn is indispensable for the induction of FNIT. We further demonstrated 

that fetal FcRn was responsible for the transplacental transport of various IgG isotypes. 

We found that anti-FcRn antibody and intravenous IgG prevented FNIT, and that 

intravenous IgG ameliorated FNIT through both FcRn-dependent and -independent 

pathways. Our data suggest that targeting FcRn may be a potential therapy for human 

FNIT as well as other maternal pathogenic antibody-mediated diseases. 


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37. [Immune thrombocytopenia--pathophysiology and treatment]. [Norwegian] 

Immunologisk trombocytopeni--patofysiologi og behandling. 

Author(s): Ghanima W, Holme PA, Tjonnfjord GE 

Citation: Tidsskrift for Den Norske Laegeforening, November 2010, vol./is. 130/21(2120- 

3), 0029-2001;0807-7096 (2010 Nov 4) 


Abstract: BACKGROUND: Immune thrombocytopenia (ITP) is caused by immune-mediated 

platelet destruction and reduced platelet production. The aim of this review article is to 

provide an updated overview of pathophysiology and new therapeutic modalities in 

ITP.MATERIAL AND METHODS: The article is based on literature identified through a nonsystematic 

search in PubMed and our own clinical experience.RESULTS: ITP is diagnosed in 

patients with platelet count < 100 x 10(9)/l after excluding other causes of 

29

thrombocytopenia. Anti-platelet autoantibodies are important in the platelet destruction 

mechanism, but other important mechanisms have been identified in recent years. 

Patients with very low platelet count < 30 x 10(9)/l are particularly susceptible to bleeding 

complications. The goal of treatment so far has been to increase the platelet count to a 

level that reduces the risk of serious bleeding. Thrombopoietin receptor agonists are new 

therapeutic agents that target the thrombopoietin receptor to increase platelet 

production. These drugs are shown to be effective in treatment of ITP.INTERPRETATION: 

New knowledge about pathophysiological mechanisms, such as sub-optimal platelet 

production in ITP, has led to the development of new therapeutic options which focus on 

stimulation of platelet production. 


38. Reconsidering fetal and neonatal alloimmune thrombocytopenia with a focus on 

screening and prevention. 

Author(s): Skogen B, Killie MK, Kjeldsen-Kragh J, Ahlen MT, Tiller H, Stuge TB, Husebekk A 

Citation: Expert Review of Hematology, October 2010, vol./is. 3/5(559-66), 1747- 

4094;1747-4094 (2010 Oct) 


Abstract: Uncertainty regarding the pathophysiology of fetal and neonatal alloimmune 

thrombocytopenia (FNAIT) has hampered the decision regarding how to identify, followup 

and treat the women and children with this potentially serious condition. Since 

knowledge of the condition is derived mainly from retrospective studies, understanding of 

the natural history of this condition remains incomplete. General screening programs for 

FNAIT have still not been introduced, mainly because of a lack of reliable risk factors and 

effective treatment. Now, several prospective screening studies involving up to 100,000 

pregnant women have been published and the results have changed the understanding of 

the pathophysiology of FNAIT and, thereby, the approach toward diagnostics, prevention 

and treatment in a more appropriate way. 


39. A retrospective analysis of obstetric patients with idiopathic thrombocytopenic 

purpura: a single center study. 

Author(s): Fujita A, Sakai R, Matsuura S, Yamamoto W, Ohshima R, Kuwabara H, Okuda M, 

Takahashi T, Ishigatsubo Y, Fujisawa S 

Citation: International Journal of Hematology, October 2010, vol./is. 92/3(463-7), 0925- 

5710;1865-3774 (2010 Oct) 


Abstract: Idiopathic thrombocytopenic purpura (ITP) commonly affects women of 

childbearing age. We studied the clinical characteristics of pregnant women with ITP to 

estimate their risks of bleeding. A retrospective chart review was performed for all 

obstetric patients with ITP who had delivery at our hospital, from 1 March 2000 to 31 

March 2008. Twenty women with ITP delivered 24 children in 23 pregnancies. In all, eight 

women were treated with corticosteroid during their pregnancy period, and there was 

only one non-responder. There was no correlation between the maternal platelet count 

and the amount of blood loss at delivery. Two infants were revealed to have had platelet 

counts lower than 30 x 109/L, and were treated with high-dose IV IgG. One of them also 

received corticosteroid therapy. There was no relationship between maternal platelet 

count at delivery and infant platelet count at birth. Overall, no serious bleeding event was 

seen in either of the mothers or infants. For most women with ITP, pregnancy is 

uncomplicated, and even those with severe thrombocytopenia during pregnancy have 

30

good outcomes when under the strict care of a hematologist and gynecologist. 


40. Bilateral retinal detachments and preeclampsia: thrombotic thrombocytopenic 

purpura or syndrome of haemolysis, elevated liver enzymes, low platelets?. 

Author(s): Mendez-Figueroa H, Davidson C 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, October 2010, vol./is. 

23/10(1268-70), 1476-4954;1476-4954 (2010 Oct) 



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systematic review. 

Author(s): Kamphuis MM, Paridaans N, Porcelijn L, De Haas M, Van Der Schoot CE, Brand 

A, Bonsel GJ, Oepkes D 

Citation: BJOG: An International Journal of Obstetrics & Gynaecology, October 2010, 

vol./is. 117/11(1335-43), 1470-0328;1471-0528 (2010 Oct) 


Abstract: BACKGROUND: [en space] Fetal and neonatal alloimmune thrombocytopenia 

(FNAIT) is a potentially devastating disease, which may lead to intracranial haemorrhage 

(ICH), with neurological damage as a consequence. In the absence of screening, FNAIT is 

only diagnosed after bleeding symptoms, with preventive options limited to a next 

pregnancy.OBJECTIVES: [en space] To estimate the population incidence of FNAIT and its 

consequences to prepare for study design of a screening programme.SEARCH STRATEGY: 

[en space] An electronic literature search using MEDLINE, EMBASE and Cochrane 

database, and references of retrieved articles. No language restrictions were 

applied.SELECTION CRITERIA: [en space] Prospective studies on screening for human 

platelet antigen 1a (HPA-1a) alloimmunisation in low-risk pregnant women.DATA 

COLLECTION AND ANALYSIS: [en space] Two reviewers independently assessed studies for 

inclusion and extracted data. Main outcome data were prevalence of HPA-1a negativity, 

HPA-1a immunisation, platelet count at birth and perinatal ICH. We aimed to compare 

outcome with and without intervention.MAIN RESULTS: [en space] HPA-1a 

alloimmunisation occurred in 294/3028 (9.7%) pregnancies at risk. Severe FNAIT occurred 

in 71/227 (31%) immunised pregnancies, with perinatal ICH in 7/71 (10%). True natural 

history data were not found because interventions were performed in most screenpositive 

women.AUTHORS' CONCLUSIONS: [en space] Screening for HPA-1a 

alloimmunisation detects about two cases in 1000 pregnancies. The calculated risk for 

perinatal ICH of 10% in pregnancies with severe FNAIT is an underestimation because 

studies without interventions were lacking. Screening of all pregnancies together with 

effective antenatal treatment such as intravenous immunoglobulin may reduce the 

mortality and morbidity associated with FNAIT. 


Full Text: 


Available in fulltext at the ULHT Library and Knowledge Services' eJournal collection ; Note: 

31

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42. Subdural haematoma in pregnancy-induced idiopathic thrombocytopenia: 

Conservative management. 

Author(s): Pandey M, Saraswat N, Vajifdar H, Chaudhary L 

Citation: Indian Journal of Anaesthesia, September 2010, vol./is. 54/5(470-1), 0019- 

5049;0976-2817 (2010 Sep) 


Abstract: Conservative management of subdural haematoma with antioedema measures 

in second gravida with idiopathic thrombocytopenic purpura (ITP) resulted in resolution of 

haematoma. We present a case of second gravida with ITP who developed subdural 

haematoma following normal vaginal delivery. She was put on mechanical ventilation and 

managed conservatively with platelet transfusion, Mannitol 1g/kg, Dexamethasone 

1mg/kg and Glycerol 10ml TDS. She regained consciousness and was extubated after 48 

hrs. Repeat CT after 10 days showed no mass effect with resolving haematoma which 

resolved completely after 15 days. Trial of conservative management is safe in pregnant 

patient with ITP who develops subdural haematoma. 


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43. Successful prevention of thrombotic thrombocytopenic purpura (TTP) relapse 

using monthly prophylactic plasma exchanges throughout pregnancy in a patient with 

systemic lupus erythematosus and a prior history of refractory TTP and recurrent fetal 

loss. 

Author(s): Abou-Nassar K, Karsh J, Giulivi A, Allan D 

Citation: Transfusion & Apheresis Science, August 2010, vol./is. 43/1(29-31), 1473- 

0502;1473-0502 (2010 Aug) 


Abstract: BACKGROUND: The occurrence of thrombotic thrombocytopenic purpura (TTP) 

in the setting systemic lupus erythematosus (SLE) is rare. In women of childbearing age, 

TTP is associated with high rates of recurrence in pregnancy. Furthermore, both TTP and 

SLE are associated with a significant risk of adverse pregnancy outcomes.CASE 

PRESENTATION: We describe the case of a 36 year old female in her first trimester of 

pregnancy with a prior history of SLE-associated severe refractory TTP who was treated 

with a combination of corticosteroids and prophylactic plasma exchanges (PLEX) 

throughout pregnancy to prevent TTP recurrence. She delivered a healthy infant at 33 

weeks of gestation after the onset of preterm labor. There was no evidence of TTP 

recurrence in the antepartum or postpartum period in this high risk patient.CONCLUSION: 

Prophylactic PLEX should be considered as a therapeutic option to prevent recurrent TTP 

during pregnancy in high risk patients, including patients with previous SLE-associated 

TTP. (c) 2010 Elsevier Ltd. All rights reserved. 


44. [Thrombotic thrombocytopenic purpura in pregnancy. Case report]. [Czech] 

Tromboticka trombocytopenicka purpura v tehotenstvi. Kazuistika. 

Author(s): Skultety J, Novackova M, Binder T, Hadacova I, Salaj P, Rob L 

32

Citation: Ceska Gynekologie, August 2010, vol./is. 75/4(306-8), 1210-7832;1210-7832 

(2010 Aug) 


Abstract: OBJECTIVE: Description of case of patient with rare thrombotic 

thrombocytopenic purpura in pregnancy.SUBJECT: Case report.SETTING: Department of 

Gynecology and Obstetrics, Charles University and University Hospital Motol, 

Prague.CONCLUSION: Thrombotic thrombocytopenic purpura (TTP) is a rare and 

substantial disorder characterized with combination of microangiopathic haemolytic 

anemia, consumption trombocytopenia and symptoms of organs dysfunction--especially 

kidneys and neurological deficiency. It's caused by production of microthrombi affecting 

small blood vessels. These palatelets-rich microtrombi are formed due to deficiency of the 

enzyme ADAMTS13--metalloprotease which is responsible for cleaving of ultralarge 

multimers of von Willebrand factor into smaller units. In our case report we describe 

patient with TTP in pregnancy. Therapy with corticosteroids and immunoglobulines was 

not effective, improvement of thrombocytopenia appeared after plasmapheresis (total 

count 14). The delivery was induced at term without complications. Target examination 

confirmed diagnosis of secondary TTP. 


45. Intracranial hemorrhage in alloimmune thrombocytopenia: stratified 

management to prevent recurrence in the subsequent affected fetus. 

Author(s): Bussel JB, Berkowitz RL, Hung C, Kolb EA, Wissert M, Primiani A, Tsaur FW, 

Macfarland JG 

Citation: American Journal of Obstetrics & Gynecology, August 2010, vol./is. 

203/2(135.e1-14), 0002-9378;1097-6868 (2010 Aug) 


Abstract: OBJECTIVE: We sought to prevent intracranial hemorrhage (ICH) through 

antenatal management of alloimmune thrombocytopenia.STUDY DESIGN: A total of 33 

women (37 pregnancies) with alloimmune thrombocytopenia and ICH in a previous child 

were stratified according to the timing of the previous child's ICH: extremely high risk (HR) 

(n = 8) had ICH

ADAMTS 13 in late pregnancy and during the postpartum period increases the risk for a 

woman to develop life-threatening thrombotic thrombocytopenic purpura (TTP). This is 

also the time of great risk for the more common obstetric complications of preeclampsia; 

eclampsia; and hemolysis, elevated liver functions tests, low platelets (HELLP) syndrome. 

These conditions are associated with high maternal and perinatal mortality. Differential 

diagnosis may be difficult due to the overlapping of clinical and laboratory findings, 

including thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, 

and renal insufficiency, making it difficult or impossible to distinguish them from TTP. 

Management of microangiopathic disorders encountered during pregnancy differ; 

therefore, an accurate diagnosis is required. Outcomes of TTP without plasma exchange 

therapy (TPE) are almost uniformly fatal. Early recognition and management of symptoms 

with prompt and aggressive TPE is essential when TTP is suspected. 


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47. A case of pregnancy-induced thrombotic thrombocytopenic purpura with a kidney 

allograft recipient. 

Author(s): Iwami D, Harada H, Hotta K, Miura M, Seki T, Togashi M, Hirano T 

Citation: Clinical Transplantation, July 2010, vol./is. 24 Suppl 22/(66-9), 0902-0063;1399- 

0012 (2010 Jul) 


Abstract: A 32-yr-old female patient, who had been suffering from diffuse crescentic 

glomerulonephritis and a consequent end-stage renal disease, successfully underwent 

living-related ABO-incompatible kidney transplantation after a desensitization therapy 

including anti-CD20 monoclonal antibody. Forty-six months after the transplantation, the 

recipient became pregnant. At the 17th gestational week, the patient was admitted for 

the management of pregnancy-induced hypertension and aggressive deterioration of 

kidney graft function. At the 21st gestational week, the patient lost her kidney graft and 

was re-induced into regular hemodialysis. The patient was also suffering from progressive 

hemolytic anemia, thrombocytopenia, and neurologic symptoms with decreased activity 

of von Willebrand factor-cleaving protease, a disintegrin-like and metalloprotease with 

thrombospondin type 1 motifs 13 (ADAMTS13). From these findings and a kidney allograft 

biopsy, the patient was diagnosed as thrombotic thrombocytopenic purpura concurrent 

with acute T-cell-mediated rejection. The patient immediately underwent plasma 

exchange as well as steroid pulse therapy. Despite these treatments, thrombocytopenia 

and intrauterine growth retardation progressed. The patient underwent a caesarian 

section at the 24th gestational week. Consequently, her platelet count recovered 

drastically. However, the patient lost her neonate five d after giving a birth, and the 

patient's graft function had never recovered. 


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48. Successful management of recurrent pregnancy-related thrombotic 

thrombocytopaenia purpura in a renal transplant recipient. 

Author(s): Lam K, Martlew V, Walkinshaw S, Alfirevic Z, Howse M 

Citation: Nephrology Dialysis Transplantation, July 2010, vol./is. 25/7(2378-80), 0931- 

34

0509;1460-2385 (2010 Jul) 


Abstract: Thrombotic thrombocytopaenic purpura (TTP) is a rare but potentially 

devastating complication of pregnancy. We report the first documented case of a 

successful treatment of recurrent TTP complicating pregnancy in a renal transplant 

patient. 


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49. Predictors for neonatal thrombocytopenia in infants of thrombocytopenic 

mothers during pregnancy. 

Author(s): Maayan-Metzger A, Leibovitch L, Schushan-Eisen I, Strauss T, Kenet G, Kuint J 

Citation: Pediatric Blood & Cancer, July 2010, vol./is. 55/1(145-8), 1545-5009;1545-5017 

(2010 Jul 15) 


Abstract: BACKGROUND: Although maternal thrombocytopenia during pregnancy is 

common, its effect on neonatal platelets has not yet been fully evaluated.METHODS: We 

retrospectively evaluated the rate of thrombocytopenia among 767 healthy term 

neonates (gestational age 37-42 weeks) born to 723 mothers with pregnancy-induced 

thrombocytopenia to define risk factors predicting thrombocytopenia in this 

group.RESULTS: Thrombocytopenia was diagnosed in 2.2% of the infants. Multivariate 

analysis showed that infants with thrombocytopenia were more likely to be male, to be 

born at lower gestational age and to have lower birth weight associated with lower 

maternal platelets counts. Maternal platelet counts of 100-149 x 10(9)/L, 50-99 x 10(9)/L, 

and

idiopathic thrombocytopenic purpura (ITP) when PLT < (20 - 30) x 10(9)/L or bleeding. PLT 

would be given if all the above management were failed, or PLT < 10 x 10(9)/L, or 

bleeding. Women without bleeding would be closely monitored and delivery would be 

planned.RESULTS: (1) Twenty-six cases were identified among 9302 deliveries during the 

study period (0.28%), with an average of maternal age of 29. Seventeen were diagnosed 

before conception and 9 during pregnancy. Among the 26 women, half received regular 

prenatal check in our hospital and the average gestations at diagnosis was 24 weeks and 

the other half without regular prenatal visits and the average gestations at diagnosis was 

32 weeks. Etiology was identified in 24 out of the 26 women, including 14 (54%) ITP, 5 

myelodysplastic syndrome (MDS), 4 chronic aplastic anaemia (CAA) and 1 systemic lupus 

erythematosus (SLE). (2) Management: All of the 26 women received blood products. 

Among the 14 ITP cases, 6 received predinisone and IVIG and 8 only took predinisone. 

Nine of the 26 patients (35%) had pregnant complications, among which 6 (6/9) were 

preeclampsia. The overall average gestation at delivery was 36 weeks. Only 2 delivered 

vaginally with the average blood loss of 83 ml and 23 cesarean sections were performed 

with the average blood loss of 410 ml. (3) Perinatal outcomes: There were 26 perinatal 

babies, among which 1 died intrauterine and 25 were born alive (12 preterm infants). The 

average birth weight was 2877 g. Neonatal severe thrombocytopenia presented in 2 

newborns whose mother complicated with ITP.CONCLUSIONS: The main cause of 

extremely severe thrombocytopenia during pregnancy is ITP, managed mainly by 

predinisone and IVIG, followed by CAA and MDS, which may require supportive 

treatment. Pregnancy complicated with extremely severe thrombocytopenia is not an 

indication of termination. Better maternal and fetal outcomes can be achieved through 

proper treatment based on the etiology, intensive care in prevention and management of 

complications and cesarean section. 


51. The use of angiogenic biomarkers to differentiate non-HELLP related 

thrombocytopenia from HELLP syndrome. 

Author(s): Young B, Levine RJ, Salahuddin S, Qian C, Lim KH, Karumanchi SA, Rana S 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, May 2010, vol./is. 23/5(366-70), 

1476-4954;1476-4954 (2010 May) 


Abstract: OBJECTIVE: Preeclampsia (PE) is diagnosed using clinical criteria and in atypical 

cases the diagnosis may be inaccurate as there are no specific tests to confirm or exclude 

PE. This study sought to evaluate the utility of angiogenic biomarkers, sFlt1, sEng and PlGF 

to distinguish patients with gestational thrombocytopenia and immune thrombocytopenic 

purpura (ITP) from patients with thrombocytopenia resulting from the HELLP (hemolysis, 

elevated liver enzymes and low platelets) syndrome, a complication of severe 

PE.METHODS: Serum was collected and the angiogenic biomarkers of patients with ITP 

and gestational thrombocytopenia (N = 9) were compared to patients with HELLP (N = 11) 

and PE (N = 11). Circulating levels of these angiogenic biomarkers were also compared by 

gestational age to 1564 randomly selected normotensive women from the Calcium for 

Preeclampsia Prevention study.RESULTS: Patients with non-HELLP thrombocytopenia had 

lower sFlt1 (7.3 +/- 3.8 ng/ml vs. 15.5 +/- 5 ng/ml, P < 0.001), lower sEng (8.7 +/- 3.6 vs. 34 

+/- 17, P < 0.001) and higher PlGF (484 +/- 412 vs. 66.3 +/- 44, P = 0.003) than patients 

with HELLP syndrome. Angiogenic factor abnormalities in patients with PE were similar to 

patients with HELLP syndrome, suggesting a common pathogenesis. Patients with non- 

HELLP thrombocytopenia had angiogenic profiles similar to normotensive controls, 

whereas patients with HELLP syndrome had levels higher than the 90th percentile for sFlt1 

and sEng and lower than the 10th percentile for PlGF.CONCLUSIONS: Angiogenic 

36

iomarkers may be useful in excluding conditions that mimic PE. 


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52. Prenatal diagnosis of fetal intracranial hemorrhage in pregnancy complicated by 

idiopathic thrombocytopenic purpura. 

Author(s): Koyama S, Tomimatsu T, Sawada K, Kanagawa T, Isobe A, Taniguchi Y, Wada T, 

Kimura T, Arahori H, Kitabatake Y, Wada K 

Citation: Prenatal Diagnosis, May 2010, vol./is. 30/5(489-91), 0197-3851;1097-0223 (2010 

May) 



53. Retrospective comparison of maternal vs. HPA-matched donor platelets for 

treatment of fetal alloimmune thrombocytopenia. 

Author(s): Giers G, Wenzel F, Fischer J, Stockschlader M, Riethmacher R, Lorenz H, 

Tutschek B 

Citation: Vox Sanguinis, April 2010, vol./is. 98/3 Pt 2(423-30), 0042-9007;1423-0410 (2010 

Apr) 


Abstract: BACKGROUND AND OBJECTIVES: In fetal alloimmune thrombocytopenia (FAIT), 

transplacental maternal antibodies cause destruction of fetal platelets. FAIT is similar to 

fetal Rhesus haemolytic disease, but half of the affected fetuses are born to primiparous 

women. In 10-20% of cases, prenatal and perinatal intracranial haemorrhages are 

reported. Different therapeutic approaches have been described, including maternally 

administered high-dose intravenous immunoglobulin (high dose IVIG) without or with 

steroids or intrauterine transfusion (IUT) of compatible platelets. For the latter, the use of 

plasma-free maternal and donor platelets has been described, but a comparison of these 

two sources of platelets has not been reported.MATERIALS AND METHODS: We 

retrospectively analyzed the clinical courses of cases with FAIT treated with IUT of either 

HPA-matched donor platelets or maternal platelets, done by a single team between 1990 

and 1997. In 57 pregnancies, FAIT was treated by repeated IUT with either maternal (15 

fetuses) or donor platelets (42 fetuses).RESULTS: There was no procedure-related fetal or 

neonatal loss. Platelets from both sources reliably raised the fetal platelet counts. Donor 

platelet preparations contained more platelets and yielded higher fetal post-transfusion 

platelet counts, but maternal platelets were clinically equally effective.CONCLUSIONS: 

Donor and maternal platelet concentrates are effective sources for the treatment of FAIT. 


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54. New low-frequency platelet glycoprotein polymorphisms associated with 

neonatal alloimmune thrombocytopenia. 

Author(s): Peterson JA, Gitter ML, Kanack A, Curtis B, McFarland J, Bougie D, Aster R 

Citation: Transfusion, February 2010, vol./is. 50/2(324-33), 0041-1132;1537-2995 (2010 

37

Feb) 


Abstract: BACKGROUND: Recent reports suggest that maternal immunization against lowfrequency, 

platelet (PLT)-specific glycoprotein (GP) polymorphisms is a more common 

cause of neonatal alloimmune thrombocytopenia (NATP) than previously thought.STUDY 

DESIGN AND METHODS: Serologic and molecular studies were performed on PLTs and 

DNA from three families in which an infant was born with apparent NATP not attributable 

to maternal immunization against known PLT-specific alloantigens.RESULTS: Antibodies 

reactive only with paternal PLTs were identified in each mother. In Cases 2 (Kno) and 3 

(Nos), but not Case 1 (Sta), antibody recognized paternal GPIIb/IIIa in solid-phase assays. 

Unique mutations encoding amino acid substitutions in GPIIb (Case 2) or GPIIIa (Cases 1 

and 3) were identified in paternal DNA and in DNA from two of the affected infants. 

Antibody from all three cases recognized recombinant GPIIIa (Case 1 [Sta] and Case 3 

[Nos]) and GPIIb (Case 2, Kno) mutated to contain the polymorphisms identified in the 

respective fathers. None of 100 unselected normal subjects possessed the paternal 

mutations. Enzyme-linked immunosorbent assay and flow cytometric studies suggested 

that failure of maternal serum from Case 1 (Sta) to react with paternal GPIIIa in solidphase 

assays resulted from use of a monoclonal antibody AP2, for antigen immobilization 

that competed with the maternal antibody for binding to the Sta epitope.CONCLUSION: 

NATP in the three cases was caused by maternal immunization against previously 

unreported, low-frequency GP polymorphisms. Maternal immunization against lowfrequency 

PLT-specific alloantigens should be considered in cases of apparent NATP not 

resolved by conventional serologic and molecular testing. 


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if required. 

55. Cerebellar loss and brain-stem atrophy associated with neonatal alloimmune 

thrombocytopenia in a discordant twin. 

Author(s): Mohila CA, Kubicka ZJ, Ornvold KT, Harris BT 

Citation: Pediatric & Developmental Pathology, January 2010, vol./is. 13/1(55-62), 1093- 

5266;1093-5266 (2010 Jan-Feb) 

Publication Date: January 2010 

Abstract: Neonatal alloimmune thrombocytopenia (NAIT) is due to an immune-mediated 

maternal-fetal platelet antigen incompatibility. Central nervous system abnormalities 

have been reported in infants with NAIT and include intracranial hemorrhage, 

ventriculomegaly, porencephalic cysts, neuronal migrational disorders, and, rarely, 

cerebellar lesions. We present the clinical and neuropathological findings from a case of a 

3-day-old diamniotic/dichorionic female twin with known bilateral ventriculomegaly born 

prematurely at 33-1/7 weeks in gestational age. The pregnancy was further complicated 

by discordant intrauterine growth, intraventricular hemorrhage in the co-twin, and NAIT. 

At birth, the infant was noted to have diffuse body ecchymoses and petechiae and 

arthrogryposis. She subsequently developed multisystem organ failure and disseminated 

intravascular coagulopathy and died on the 3rd day of life. Neuropathological findings at 

autopsy included a posterior fossa cyst with no gross anatomic evidence of a cerebellum, 

atrophic pons and medulla with prominent pyramidal tracts and absent olivary nuclei, 

thinned corpus callosum, and symmetrical dilation of bilateral lateral ventricles. 

38

Microscopic examination confirmed the gross findings and revealed no histological 

evidence of cerebellar tissue, absence of superior and inferior cerebellar peduncles, and 

acute and chronic germinal matrix hemorrhages. Immunohistochemical studies revealed a 

focus of reactive gliosis at the base of the posterior fossa cyst with no evidence of 

cerebellar Purkinje or granule cells. To our knowledge, this is the 1st report with wellcharacterized 

neuropathological examination detailing complete cerebellar loss and brainstem 

atrophy in a neonate with NAIT. 


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56. Successful pregnancy in a case of congenital thrombotic thrombocytopenic 

purpura. 

Author(s): Meti S, Paneesha S, Patni S 

Citation: Journal of Obstetrics & Gynaecology, 2010, vol./is. 30/5(519-21), 0144- 

3615;1364-6893 (2010) 

Publication Date: 2010 


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57. Perinatal management of immune thrombocytopenic purpura--a case report and 

review of literature. 

Author(s): Gupta RS, Rajaram S, Bharadwaj P, Goel N, Singh KC, Bisht S 

Citation: Journal of the Indian Medical Association, January 2010, vol./is. 108/1(42, 47-8), 

0019-5847;0019-5847 (2010 Jan) 


Abstract: Immune thrombocytopenic purpura is principally a disease of young women. 

Therefore it may often be associated with pregnancy. It is commonly complicated by 

abortion, intra-uterine growth retardation and neonatal intracranial haemorrhage so that 

perinatal mortality may be as high as 20%. Hence perinatal management of immune 

thrombocytopenic purpura should include maintenance of maternal platelet count and 

regular monitoring of foetal growth along with prediction and prevention of foetal passive 

immune thrombocytopenia. Determination of foetal platelet count in certain situations 

may help in concomitant selection of delivery mode. The following case report emphasises 

the importance of diagnosing this condition at peripheral healthcare level so that 

perinatal outcome can be markedly improved. 


58. Treatment of idiopathic thrombocytopenic purpura in pregnancy with pulsed dose 

of dexamethasone. 

Author(s): Grgic O, Ivanisevic M, Delmis J 

Citation: Journal of Obstetrics & Gynaecology, 2010, vol./is. 30/8(864), 0144-3615;1364- 

6893 (2010) 



39

Full Text: 


59. Pregnancy-associated thrombotic thrombocytopenic purpura with anticentromere 

antibody-positive Raynaud's syndrome. 

Author(s): Watanabe R, Shirai T, Tajima Y, Ohguchi H, Onishi Y, Fujii H, Takasawa N, Ishii T, 

Harigae H 

Citation: Internal Medicine, 2010, vol./is. 49/12(1229-32), 0918-2918;1349-7235 (2010) 


Abstract: Thrombotic thrombocytopenic purpura (TTP), scleroderma renal crisis (SRC), and 

hemolysis, elevated liver enzyme levels, and a low platelet count (HELLP) syndrome 

display common symptoms that include microangiopathic hemolytic anemia, 

thrombocytopenia, and renal failure. Therefore, it is important to distinguish between 

them because their treatments vary: however, the differential diagnosis is sometimes 

difficult. We report a 32-year-old woman who was referred to our department for further 

examination of microangiopathic hemolytic anemia, thrombocytopenia, and a slightly 

elevated serum creatinine level with anti-centromere antibody-positive Raynaud's 

syndrome in the early puerperal period. TTP, SRC, and HELLP syndrome were considered 

in the differential diagnosis, but the measurement of a disintegrin-like metalloprotease 

with thrombospondin type 1 motifs 13 (ADAMTS 13) activity and its inhibitor level led to 

the diagnosis of TTP. She was successfully treated by plasma exchange and high-dose 

prednisolone and angiotensin-converting enzyme inhibitor. If microangiopathic hemolytic 

anemia and thrombocytopenia are observed in perinatal women or patients with signs of 

systemic sclerosis, the measurement of ADAMTS13 activity and its inhibitor level are 

essential for diagnosis and therapeutic choice. 


60. Anticoagulation with argatroban in a parturient with heparin-induced 


Author(s): Ekbatani A, Asaro LR, Malinow AM 

Citation: International Journal of Obstetric Anesthesia, January 2010, vol./is. 19/1(82-7), 

0959-289X;1532-3374 (2010 Jan) 


Abstract: Unfractionated heparin and low-molecular-weight heparin are currently the 

anticoagulants of choice for the prevention of recurrent thromboembolic disease during 

pregnancy. However, heparin-induced thrombocytopenia contraindicates the use of 

unfractionated heparin and low-molecular-weight heparin. We describe a patient who 

was admitted to our hospital with deep vein thrombosis at 18 weeks of gestation and who 

developed heparin-induced thrombocytopenia during her antenatal care. Therapeutic 

anticoagulation was initially achieved with argatroban, then changed to fondaparinux. 

During early labor, fondaparinux was discontinued and intravenous argatroban was 

substituted. Argatroban was discontinued during transition to active labor. After return of 

a normal partial thromboplastin time, combined spinal-epidural analgesia was induced for 

routine completion of labor and vaginal delivery. We discuss the decisions made in the 

maintenance of this patient's anticoagulation during the peripartum period as well as 

timing of her neuraxial labor analgesia. Copyright 2009 Elsevier Ltd. All rights reserved. 


61. The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture 

40

in thrombocytopenic individuals. 

Author(s): van Veen JJ, Nokes TJ, Makris M 

Citation: British Journal of Haematology, January 2010, vol./is. 148/1(15-25), 0007- 

1048;1365-2141 (2010 Jan) 


Abstract: Neuraxial anaesthesia is increasingly performed in thrombocytopenic patients at 

the time of delivery of pregnancy. There is a lack of data regarding the optimum platelet 

count at which spinal procedures can be safely performed. Reports are often confounded 

by the presence of other risk factors for spinal haematomata, such as anticoagulants, 

antiplatelet agents and other acquired or congenital coagulopathies/platelet function 

defects or rapidly falling platelet counts. In the absence of these additional risk factors, a 

platelet count of 80 x 10(9)/l is a 'safe' count for placing an epidural or spinal anaesthetic 

and 40 x 10(9)/l is a 'safe' count for lumbar puncture. It is likely that lower platelet counts 

may also be safe but there is insufficient published evidence to make recommendations 

for lower levels at this stage. For patients with platelet counts of 50-80 x 10(9)/l requiring 

epidural or spinal anaesthesia and patients with a platelet count 20-40 x 10(9)/l requiring 

a lumbar puncture, an individual decision based on assessment of risks and benefits 

should be made. 


Full Text: 


62. Neonatal outcomes of pregnancy complicated by idiopathic thrombocytopenic 

purpura. 

Author(s): Ozkan H, Cetinkaya M, Koksal N, Ali R, Gunes AM, Baytan B, Ozkalemkas F, 

Ozkocaman V, Ozcelik T, Gunay U, Tunali A, Kimya Y, Cengiz C 

Citation: Journal of Perinatology, January 2010, vol./is. 30/1(38-44), 0743-8346;1476-5543 

(2010 Jan) 


Abstract: OBJECTIVE: The aim of this study was to determine the factors associated with 

the prognosis of newborns born to mothers with idiopathic thrombocytopenic purpura 

(ITP), and to compare the infants with/without thrombocytopenia in terms of maternal 

and neonatal characteristics.STUDY DESIGN: We reviewed the charts of 29 parturients 

with ITP and their newborns who were born between January 1998 and December 

2008.RESULT: A total of 16 (55%) gravidas had been diagnosed with ITP before pregnancy 

and 13 (45%) were diagnosed during pregnancy. Thrombocytopenia was observed in 21 

gravidas. In total, 17 (58%) gravidas received treatment to increase the platelet count. The 

majority of deliveries (72.5%) were vaginal. The infant platelet counts at birth ranged from 

20 to 336 x 10(9) per liter. None of the neonates had complications attributable to the 

mode of delivery. Normal platelet counts were determined in 15 newborns, whereas 14 

infants had thrombocytopenia at birth. Three (10.3%) neonates had mild, four neonates 

(13.7%) had moderate and seven neonates (24.1%) had severe thrombocytopenia. The 

age of the mothers having infants with thrombocytopenia was significantly higher (30+/- 

5.3 vs 25.3+/-3.8 years), most of the infants (10/14 (71%)) were males 

(P


63. International consensus report on the investigation and management of primary 

immune thrombocytopenia. 

Author(s): Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong 

BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, 

McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ 

Citation: Blood, January 2010, vol./is. 115/2(168-86), 0006-4971;1528-0020 (2010 Jan 14) 


Abstract: Previously published guidelines for the diagnosis and management of primary 

immune thrombocytopenia (ITP) require updating largely due to the introduction of new 

classes of therapeutic agents, and a greater understanding of the disease 

pathophysiology. However, treatment-related decisions still remain principally dependent 

on clinical expertise or patient preference rather than high-quality clinical trial evidence. 

This consensus document aims to report on new data and provide consensus-based 

recommendations relating to diagnosis and treatment of ITP in adults, in children, and 

during pregnancy. The inclusion of summary tables within this document, supported by 

information tables in the online appendices, is intended to aid in clinical decision making. 


Full Text: 


64. A Case of HELLP Syndrome in a Patient with Immune Thrombocytopenic Purpura. 

Author(s): Ben S, Rodriguez F, Severo C, Debat N 

Citation: Obstetrics & Gynecology International, 2010, vol./is. 2010/, 1687-9597 (2010) 


Abstract: We will describe the clinical case of a pregnant patient with chronic Immune 

Thrombocytopenic Purpura who develops preeclampsia syndrome with HELLP syndrome. 

These concomitant and independent conditions become complex, resulting in 

thrombocytopenia which creates diagnostic, prognostic and therapeutic inconveniences. 


Full Text: 



Author(s): McCrae KR 

Citation: Hematology, 2010, vol./is. 2010/(397-402), 1520-4383;1520-4383 (2010) 


Abstract: Thrombocytopenia occurs commonly during pregnancy, and may result from 

diverse etiologies. Awareness of these many causes facilitates proper diagnosis and 

management of thrombocytopenia in the pregnant setting. Some causes of 

thrombocytopenia are unique to pregnancy and may not be familiar to hematologists. In 

the review, we will discuss the differential diagnosis of thrombocytopenia in pregnancy, 

and the pathogenesis of selected thrombocytopenic disorders. Considerations for optimal 

management of the pregnant patient with thrombocytopenia will also be described. 

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66. Immune thrombocytopenia in pregnancy. 

Author(s): Stavrou E, McCrae KR 

Citation: Hematology - Oncology Clinics of North America, December 2009, vol./is. 

23/6(1299-316), 0889-8588;1558-1977 (2009 Dec) 


Abstract: Management of immune thrombocytopenia in pregnancy can be a complex and 

challenging task and may be complicated by fetal-neonatal thrombocytopenia. Although 

fetal intracranial hemorrhage is a rare complication of immune thrombocytopenia in 

pregnancy, invasive studies designed to determine the fetal platelet count before delivery 

are associated with greater risk than that of fetal intracranial hemorrhage and are 

discouraged. Moreover, the risk of neonatal bleeding complications does not correlate 

with the mode of delivery, and cesarean section should be reserved only for obstetric 

indications. 


67. Prenatal treatment of fetomaternal thrombocytopenia. 

Author(s): Vatopoulou T, Sorinola O 

Citation: British Journal of Hospital Medicine, November 2009, vol./is. 70/11(660-1), 1750- 

8460;1750-8460 (2009 Nov) 



Full Text: 


Available in print at Lincoln County Hospital Professional Library 

68. Perinatal outcomes and complications of pregnancy in women with immune 


Author(s): Belkin A, Levy A, Sheiner E 

Citation: Journal of Maternal-Fetal & Neonatal Medicine, November 2009, vol./is. 

22/11(1081-5), 1476-4954;1476-4954 (2009 Nov) 


Abstract: OBJECTIVE: To investigate pregnancy and perinatal outcomes in women with 

immune thrombocytopenic purpura (ITP).METHODS: A retrospective study comparing all 

singleton pregnancies of women with and without ITP was conducted. Deliveries occurred 

between the years 1988 and 2007. Multiple logistic regression models were performed to 

control for confounders.RESULTS: During the study period, 186,602 deliveries were 

recorded, out of which 104 (0.06%) occurred in patients with ITP. In a multivariable 

analysis, we found the following conditions to be significantly and independently 

associated with ITP: hypertensive disorders, diabetes mellitus, and preterm delivery (

0.011) when compared with patients without ITP. Two multivariable logistic regression 

models were constructed with perinatal mortality and preterm delivery (


71. Limitations of ADAMTS-13 activity level in diagnosing thrombotic 

thrombocytopenic purpura in pregnancy. 

Author(s): Ehsanipoor RM, Rajan P, Holcombe RF, Wing DA 

Citation: Clinical & Applied Thrombosis/Hemostasis, October 2009, vol./is. 15/5(585-7), 

1076-0296;1938-2723 (2009 Oct) 


Abstract: In pregnancy, it may be difficult to differentiate the syndrome of hemolysis, 

elevated liver enzymes, and low platelets from thrombotic thrombocytopenia purpura. 

Severely depressed (35 

weeks were allocated into general anesthesia group (35 cases) and local anesthesia group 

(30 cases) randomly. The time from skin incision to fetal delivery, the oxyhemoglobin 

saturation (SO2) before and after anesthesia, the blood loss during operation, Apgar 

scores at 1 min, birth weight,umbilical cord blood gas analysis were recorded.RESULTS: 

The mean time from anesthesia induction to fetal delivery was (9.7 +/- 3.5) minutes in 

general anesthesia group. The time from skin incision to fetal delivery in general 

anesthesia group [(7.7 +/- 2.5) minutes] was shorter than that in local anesthesia group 

[(12.5 +/- 3.0) minutes, P < 0.01], while the operation time had no significant differences. 

There were no significant difference for the value of SO2 before and after general 

anesthesia or local anesthesia (P > 0.05). There was no significant difference for the blood 

loss [(471 +/- 245) ml vs. (452 +/- 213) ml, P > 0.05], Apgar scores at 1 minute, birth weight 

and umbilical cord blood gas analysis between the two groups (P > 0.05). There had two 

infants with blue asphyxia in local anesthesia group while no infant with asphyxia in 

general anesthesia group.CONCLUSION: General anesthesia is safe to pregnant women 

with thrombocytopenia during CS. 

45


73. Successful use of danaparoid in two pregnant women with heart valve prosthesis 

and heparin-induced thrombocytopenia Type II (HIT). 

Author(s): Gerhardt A, Scharf RE, Zotz RB 

Citation: Clinical & Applied Thrombosis/Hemostasis, July 2009, vol./is. 15/4(461-4), 1076- 

0296;1076-0296 (2009 Jul-Aug) 


Abstract: Anticoagulant therapy with heparin for the prevention of thromboembolism in 

pregnant women with prosthetic heart valves is associated with an increased risk to the 

mother and/or the fetus. A life-threatening complication of the therapy with heparin is 

heparin-induced thrombocytopenia type II (HIT). danaparoid has not yet been reported to 

be safe and effective for this indication. This study reports on a 26-year-old woman with 

tricuspidal valve prosthesis and a 37-year-old woman with a St. Jude Medical mitral valve 

prosthesis who were anticoagulated with danaparoid during pregnancy because of HIT. 

Anti-Xa levels were between 0.6 and 1.2 IU/mL during pregnancy with target levels of 1.0 

IU/mL. Cesarean section was performed at anti-Xa levels of 0.3 and 0.7 IU/mL. One 

woman developed a placental hematoma at the 32nd week of gestation, which did not 

increase over the following week. Both patients delivered healthy boys. Heparin-induced 

thrombocytopenia in pregnant women with prosthetic heart valve can be successfully 

managed with danaparoid. 


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74. Diagnosis and management of the fetus and neonate with alloimmune 


Author(s): Bussel J 

Citation: Journal of Thrombosis & Haemostasis, July 2009, vol./is. 7 Suppl 1/(253-7), 1538- 

7836;1538-7836 (2009 Jul) 


Abstract: Fetal and neonatal alloimmune thrombocytopenia (AIT) is the commonest cause 

of severe thrombocytopenia in neonates, and of intracranial hemorrhage (ICH) in term 

neonates [1] (J Trop Pediatr, 1999; 45: 237). If a newborn is affected with AIT, the next 

child will likely be more severely affected, and therefore fetal thrombocytopenia will 

begin early in gestation [2, 3] (Arch Neurol, 1984; 41: 30; N Engl J Med 1997; 337: 22). This 

creates a risk of in utero ICH even if there was not one in the previous pregnancy. There 

are new developments in AIT in regard to diagnosis, treatment, and screening which will 

be the focus of this review. 


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75. Idiopathic thrombocytopaenic purpura in pregnancy presenting with lifethreatening 

epistaxis. 

Author(s): Bukar M, Audu BM, Bako BG, Garandawa HI, Kagu MB 

Citation: Journal of Obstetrics & Gynaecology, July 2009, vol./is. 29/5(439-40), 0144- 

46

3615;1364-6893 (2009 Jul) 



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76. Neonatal alloimmune thrombocytopenia and neutropenia associated with 

maternal human leukocyte antigen antibodies. 

Author(s): Gramatges MM, Fani P, Nadeau K, Pereira S, Jeng MR 

Citation: Pediatric Blood & Cancer, July 2009, vol./is. 53/1(97-9), 1545-5009;1545-5017 

(2009 Jul) 


Abstract: Neonatal thrombocytopenia or neutropenia may result from passive transfusion 

of maternally derived antibodies. Antibodies against platelet antigens are commonly 

associated with neonatal alloimmune thrombocytopenia (NAIT), and anti-neutrophil 

antibodies are frequently identified in alloimmune neonatal neutropenia (ANN). 

Combined alloimmune cytopenias in the newborn are rarely reported; even fewer reports 

document human leukocyte antigen (HLA) antibodies as a potential cause of neonatal 

thrombocytopenia or neutropenia. We describe neutropenia and thrombocytopenia in a 

newborn associated with markedly elevated maternal HLA antibodies in the absence of 

anti-neutrophil or anti-platelet antibodies to highlight consideration of HLA antibodies in 

the pathogenesis of ANN and NAIT. Copyright 2009 Wiley-Liss, Inc. 


77. The relationship of anti-HPA-1a amount to severity of neonatal alloimmune 

thrombocytopenia - Where does it stand?. 

Author(s): Bessos H, Killie MK, Seghatchian J, Skogen B, Urbaniak SJ 

Citation: Transfusion & Apheresis Science, April 2009, vol./is. 40/2(75-8), 1473-0502;1473- 

0502 (2009 Apr) 


Abstract: The issue of whether or not antibody quantity during pregnancy is related to 

severity of neonatal alloimmune thrombocytopenia remains unresolved. In this article we 

cite studies in support of both sides of the argument and highlight some of the reasons 

that may lie behind the observed differences amongst those studies. It may well be that 

some of the reasons for the discrepant results could be due to the type of study carried 

out (eg retrospective versus prospective), the sample size, the timing of antibody 

sampling, and possibly the type or protocol of assay used. Another major reason is the 

absence, until recently, of an international anti-HPA-1a standard. 


78. The diagnostic dilemma of thrombotic thrombocytopenic purpura/hemolytic 

uremic syndrome in the obstetric triage and emergency department: lessons from 4 

tertiary hospitals. 

Author(s): Stella CL, Dacus J, Guzman E, Dhillon P, Coppage K, How H, Sibai B 

Citation: American Journal of Obstetrics & Gynecology, April 2009, vol./is. 200/4(381.e1- 

6), 0002-9378;1097-6868 (2009 Apr) 

47


Abstract: OBJECTIVE: We report a series of occurrences of thrombotic thrombocytopenic 

purpura (TTP)/hemolytic uremic syndrome (HUS) in pregnancy that emphasizes early 

diagnosis.STUDY DESIGN: Fourteen pregnancies with TTP (n = 12) or HUS (n = 2) were 

studied. Analysis focused on clinical and laboratory findings on examination, initial 

diagnosis, and treatment.RESULTS: There were 14 pregnancies in 12 patients; 2 cases of 

TTP were diagnosed as recurrent. Five women were admitted to the emergency 

department (ED), and 7 patients were admitted to an obstetrics triage. Patients who were 

evaluated by an obstetrician were treated initially for hemolysis, elevated liver enzymes 

and low platelets syndrome/preeclampsia, whereas patients who were seen in the ED had 

a diagnosis that is commonplace in the ED (panic attack, domestic violence, 

gastroenteritis). Latency from the onset of symptoms to diagnosis ranged from 1-7 days. 

Plasmapheresis treatments in early gestation resulted in favorable maternal-neonatal 

outcome. Maternal and perinatal mortality rates were 25% each.CONCLUSION: TTP/HUS is 

a challenging diagnosis in obstetric triage and ED areas. We propose a management 

scheme that suggests how to triage patients for early diagnosis in pregnancy. 


79. [Anesthetic management in a pregnant woman suffering from idiopathic 

thrombocytopenic purpura]. [Spanish] Manejo anestesico en gestante afecta de purpura 

trombocitopenica idiopatica. 

Author(s): Raynard Ortiz M, Jamart V, Cambray C, Borras R, Mailan J 

Citation: Revista Espanola de Anestesiologia y Reanimacion, March 2009, vol./is. 

56/3(185-8), 0034-9356;0034-9356 (2009 Mar) 


Abstract: Idiopathic thrombocytopenic purpura is an autoimmune disorder characterized 

by a low platelet count. Onset usually occurs during adolescence with episodes of 

cutaneous and mucosal bleeding. Thrombocytopenia during pregnancy is associated with 

many diseases, of which idiopathic thrombocytopenic purpura is the most common in the 

first trimester. The need for treatment will depend on the platelet count and whether 

there is bleeding. At the end of pregnancy, however, whether delivery is vaginal or by 

cesarean, more aggressive therapeutic measures are required. Anesthetic management in 

this type of patient will be determined by coagulation status and platelet count, and local 

or regional anesthesia may be contraindicated. We report the case of a pregnant woman 

with idiopathic thrombocytopenic purpura who was admitted to the emergency 

department of our hospital with suspected preeclampsia. 


80. Regional anesthesia and non-preeclamptic thrombocytopenia: time to re-think 

the safe platelet count. 

Author(s): Tanaka M, Balki M, McLeod A, Carvalho JC 

Citation: Revista Brasileira de Anestesiologia, March 2009, vol./is. 59/2(142-53), 0034- 

7094;1806-907X (2009 Mar-Apr) 


Abstract: BACKGROUND AND OBJECTIVES: Although regional anesthesia is widely used for 

pain control in obstetrics, it may not be appropriate for patients with thrombocytopenia 

due to the risk of neuraxial hematoma. There is no strong evidence to suggest the 

minimum platelet count that is necessary to ensure the safe practice of regional 

anesthesia. The purpose of this study was to review the safety of regional anesthesia in 

48

non-preeclamptic thrombocytopenic parturients at our institution over a 5-year 

period.METHODS: A retrospective chart review was performed in all the non-preeclamptic 

obstetric patients who delivered at our facility between April 2001 and March 2006, and 

had platelet counts < 100 x 10(9).L(-1) on the day of anesthesia. The etiology of the 

thrombocytopenia, type of anesthesia, mode of delivery and major anesthetic 

complications were noted.RESULTS: Seventy-five patients were identified, 47 of whom 

(62.6%) had received regional anesthesia. The etiology of their thrombocytopenia was 

immune thrombocytopenic purpura in 49 patients, gestational thrombocytopenia in 20 

and other causes in 6 patients. Regional anesthesia was administered in 91.9% of the 

patients with platelet counts of 80 to 99 x 10(9).L(-1) and in 48.1% of the patients with 

platelet counts of 50 to 79 x 10(9).L(-1). None of the 11 patients with platelet counts 

below 50 x 10(9).L(-1) received regional anesthesia. There were no neurological 

complications.CONCLUSIONS: In our series, regional anesthesia was safely administered in 

pregnant patients with platelet counts between 50-79 x 10(9).L(-1). Our results are in 

keeping with other series in the literature. We suggest that in non-preeclamptic patients 

with stable platelet counts and no history or clinical signs of bleeding, the lower limit of 

platelet count for regional anesthesia should be 50 x 10(9).L(-1). 


81. Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in 

Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients. 

Author(s): Fujimura Y, Matsumoto M, Kokame K, Isonishi A, Soejima K, Akiyama N, 

Tomiyama J, Natori K, Kuranishi Y, Imamura Y, Inoue N, Higasa S, Seike M, Kozuka T, Hara 

M, Wada H, Murata M, Ikeda Y, Miyata T, George JN 

Citation: British Journal of Haematology, March 2009, vol./is. 144/5(742-54), 0007- 

1048;1365-2141 (2009 Mar) 


Abstract: Upshaw-Schulman syndrome (USS) is a congenital thrombotic thrombocytopenic 

purpura (TTP) due to mutations in the gene that encodes for ADAMTS13 (ADAMTS13), but 

its clinical signs may be mild or absent during childhood. We have identified 37 patients 

with USS (24 females, 13 males) belonging to 32 families. The nine women from six 

families who were diagnosed during their first pregnancy are the focus of this report. Six 

of the nine women had episodes of thrombocytopenia during childhood misdiagnosed as 

idiopathic thrombocytopenic purpura. Thrombocytopenia occurred during the secondthird 

trimesters in each of their 15 pregnancies, with 16 babies (one twin pregnancy), 

often followed by TTP. Of 15 pregnancies, eight babies were stillborn or died soon after 

birth, and the remaining seven were all premature except one, who was born naturally 

following plasma infusions to the mother that had started at 8 weeks' gestation. All nine 

USS women had severely deficient ADAMTS13 activity. ADAMTS13 analyses demonstrated 

that eight women were compound heterozygotes of Y304C/G525D (2 siblings), 

R125VfsX6/Q1302X (2 siblings), R193W/R349C (2 siblings), I178T/Q929X, and 

R193W/A606P; one woman was homozygous for R193W. Only the R193W mutation has 

been previously reported. These observations emphasize the importance of measuring 

ADAMTS13 activity in the evaluation of thrombocytopenia during childhood and 

pregnancy. 


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82. Thrombotic thrombocytopenic purpura in the first trimester and successful 

49

pregnancy. 

Author(s): Trisolini SM, Capria S, Gozzer M, Pupella S, Foa R, Mazzucconi MG, Meloni G 

Citation: Annals of Hematology, March 2009, vol./is. 88/3(287-9), 0939-5555;1432-0584 

(2009 Mar) 



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83. Current approaches to the evaluation and management of the fetus and neonate 

with immune thrombocytopenia. 

Author(s): Bussel JB, Sola-Visner M 

Citation: Seminars in Perinatology, February 2009, vol./is. 33/1(35-42), 0146-0005;1558- 

075X (2009 Feb) 


Abstract: Fetal and neonatal alloimmune thrombocytopenia is not a well-known disease, 

except among specialists in maternal-fetal medicine, neonatologists, and certain 

pediatricians (ie, hematologists). However, this is by far the most common cause of early 

severe thrombocytopenia in neonates and of intracranial hemorrhage in term neonates. 

In addition, if a newborn is affected with alloimmune thrombocytopenia, the next child in 

the family will likely be more severely affected. Thus, the accurate diagnosis and 

appropriate management of this disorder are of extreme importance in perinatal 

medicine and will constitute the focus of this review. 


84. Pregnancy-associated thrombotic thrombocytopenic purpura. 

Author(s): Gerth J, Schleussner E, Kentouche K, Busch M, Seifert M, Wolf G 

Citation: Thrombosis & Haemostasis, February 2009, vol./is. 101/2(248-51), 0340- 

6245;0340-6245 (2009 Feb) 


Abstract: Thrombocytopenia during pregnancy is a common diagnostic and management 

problem. Several differential diagnosis must be considered including manifestations of 

thrombotic thrombocytopenic purpura (TTP). We report here on a case of a 21-year-old 

pregnant woman who presented initially severe thrombocytopenia (8 Gpt/l) in the 

20(th)+1 week of gestation. The patient had an antibody against ADAMTS13, and enzyme 

activity was

Citation: Journal of Obstetrics & Gynaecology, February 2009, vol./is. 29/2(143), 0144- 

3615;1364-6893 (2009 Feb) 



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86. Therapeutic approaches to secondary immune thrombocytopenic purpura. 

Author(s): Bussel JB 

Citation: Seminars in Hematology, January 2009, vol./is. 46/1 Suppl 2(S44-58), 0037- 

1963;0037-1963 (2009 Jan) 


Abstract: Secondary thrombocytopenia is similar to primary or idiopathic 

thrombocytopenia (ITP) in that it is characterized by reduced platelet production or 

increased platelet destruction resulting in platelet levels

not commonly done, as it poses significant risks to the fetus. Furthermore, appropriate 

antenatal treatment of neonates is controversial. We describe the case of a 32-year-old 

woman with chronic severe ITP and a previous severely affected infant, pregnant with 

trichorionic triplets, who was successfully managed with the use of weekly intravenous 

immunoglobulin 1 g/kg without recourse to direct fetal sampling. (c) 2009 S. Karger AG, 

Basel. 


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89. Medical treatments for idiopathic thrombocytopenic purpura during pregnancy. 

Author(s): Marti-Carvajal AJ, Pena-Marti GE, Comunian-Carrasco G 

Citation: Cochrane Database of Systematic Reviews, 2009, vol./is. /4(CD007722), 1361- 

6137;1469-493X (2009) 


Abstract: BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a common 

hematologic disorder caused by immune-mediated thrombocytopenia. The magnitude of 

the maternal-fetal risk of ITP during pregnancy is controversial. Labour management of 

pregnant women with ITP remains controversial. Management of ITP during pregnancy is 

complex because of the disparity between maternal and fetal platelet counts.OBJECTIVES: 

To assess the effectiveness and safety of corticosteroids, intravenous immunoglobulin, 

vinca alkaloids, danazol, dapsone, and any other types of pharmacological treatments for 

the treatment of idiopathic thrombocytopenic purpura during pregnancy.SEARCH 

STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register 

(February 2009), LILACS (1982 to 8 February 2009), ClinicalTrials.gov (8 February 2009), 

Current Controlled Trials (16 February 2009), Google Scholar (16 February 2009) and 

ongoing and unpublished trials cited in the reference lists of relevant articles.SELECTION 

CRITERIA: Randomised controlled trials (RCTs) on any medical treatments for idiopathic 

thrombocytopenia purpura during pregnancy.DATA COLLECTION AND ANALYSIS: Two 

review authors independently evaluated methodological quality and extracted trial data. 

Any disagreement was resolved by discussion or by consulting a third review author.MAIN 

RESULTS: This review included one RCT in which 38 women (41 pregnancies) were 

randomised, with only 26 women (28 pregnancies) being analysed.This RCT comparing the 

effect of betamethasone (1.5 mg/day) with no medication found no statistically significant 

difference in neonatal thrombocytopenia (risk ratio (RR) 1.12, 95% confidence interval (CI) 

0.62 to 2.05) and neonatal bleeding (RR 1.00, 95% CI 0.24 to 4.13). Review authors 

conducted an intention-to-treat analysis which showed similar findings: RR 1.18, 95% CI 

0.57 to 2.45 and RR 1.05, 95% CI 0.24 to 4.61, respectively. Maternal death, perinatal 

mortality, postpartum haemorrhage and neonatal intracranial haemorrhage were not 

studied by this RCT.AUTHORS' CONCLUSIONS: Current evidence indicates that compared 

to no medication, betamethasone did not reduce the risk of neonatal thrombocytopenia 

and neonatal bleeding in ITP during pregnancy. There is insufficient evidence to support 

the use of betamethasone for treating ITP. This Cohrane review does not provide evidence 

about other medical treatments for ITP during pregnancy. This systematic review also 

identifies the need for well-designed, adequately powered randomised clinical trials for 

this medical condition during pregnancy. Unless randomised clinical trials provide 

evidence of a treatment effect and the trade off between potential benefits and harms 

are established, policy-makers, clinicians, and academics should not use betamethasone 

for ITP in pregnant women. Any future trials on medical treatments for treating ITP during 

pregnancy should test a variety of important maternal, neonatal or both outcome 

measures, including maternal death, perinatal mortality, postpartum haemorrhage and 

52

neonatal intracranial haemorrhage. 


Full Text: 


90. [Therapeutic approach in pregnant women with an autoimmune 

thrombocytopenic purpura]. 

Author(s): Christova R, Lisichkov T, Chernev T 

Citation: Akusherstvo i Ginekologiia, 2009, vol./is. 48/6(53-4), 0324-0959;0324-0959 

(2009) 


Abstract: The case presented herein aim to update the existing information about the 

common diagnostic problems and therapeutic approach in pregnant women that have 

autoimmune thrombocytopenic purpura (ATP). 


91. [Autoimmune thrombocitopenic purpura in pregnancy]. 

Author(s): Christova R, Lisichkov T, Chernev T 

Citation: Akusherstvo i Ginekologiia, 2009, vol./is. 48/6(42-6), 0324-0959;0324-0959 

(2009) 


Abstract: The author deals with haematologists' and obstetricians' current views on 

acquired ATP in children and adults, characterised by a transient, acute or chronic 

decrease in platelets count (


Abstract: We present the case of a woman with congenital ADAMTS13 deficiency and 

discuss peripartum management of her fourth pregnancy. All four pregnancies were 

complicated by significant thrombocytopenia. Her first pregnancy ended with fetal demise 

ascribed to HELLP syndrome and placental abruption. During her second pregnancy, she 

was diagnosed with idiopathic thrombocytopenic purpura. Thrombotic thrombocytopenic 

purpura and congenital ADAMTS13 deficiency were diagnosed during the third pregnancy. 

She had recurrent thrombotic thrombocytopenic purpura during the fourth pregnancy 

and responded to treatment with fresh frozen plasma, with a successful outcome. The 

need for accurate diagnosis to ensure appropriate treatment is emphasized. 


EMBASE results 

1. Fetal/neonatal alloimmune thrombocytopenia (FNAIT) 

Author(s): Husebekk A. 

Citation: Vox Sanguinis, December 2011, vol./is. 101/(1), 0042-9007 (December 2011) 


Abstract: Thrombocytopenia is detected in around one percent of newborns. In otherwise 

healthy term newborns, thrombocytopenia is most often caused by alloantibodies 

transferred from the mother to the foetus. Placental transfer of IgG There is an active 

transfer of IgG antibodies from the mother to the foetus based on FcRn receptors on 

throphoblasts. The obvious benefit for the foetus is protection from infections in utero 

and in the first period after birth. The transfer is by no means based on the specificity of 

the IgG molecules and in case of maternal reacting with antigens on foetal cells and 

tissues, these are also transferred. Anti-platelet antibodies Platelets have many 

polymorphic surface molecules. The most polymorphic are the HLA class I molecules. In 

addition, there are polymorphisms in the glycoproteins; altogether 17 biallelic systems of 

human platelet proteins (HPA) have been described. The amino acid differences are based 

on single nucleotide polymorphisms. Alloimmunization may take place during pregnancy 

or upon blood transfusions. The most immunogenic is the HPA-1a epitope. Since the 

genetic background differs among ethnic groups, the pattern of immunization differs. In 

China and Japan, almost all individuals are HPA-1a and alloimmunization with this antigen 

is almost absent. Whereas the HPA-4b antigen is absent in Western countries, it is more 

frequently found in Japan and China and immunization with the HPA-4a antigen takes 

place. Fetal/neonatal alloimmune thrombocytopenia (FNAIT) FNAIT is most often 

diagnosed after birth of a child with thrombocytopenia and bleeding symptoms. 

Alloimmune thrombocytopenia is found in 1:1000-2000 newborn, around 30% of the 

newborns have severe thrombocytopenia (

standard follow-up procedure due to reports of severe complications. Future 

management of FNAIT Results from prospective studies have shown that FNAIT is more 

similar to haemolytic disease of the newborn (HDN) than thought before. Also, treatment 

with IVIg in the pregnancy and careful delivery and transfusion of platelet to the newborn, 

reduce morbidity and mortality of FNAIT. Several reports conclude that general screening 

should be introduced. Also, there are studies of prophylaxis (anti-HPA-1a antibodies) 

aiming at preventing immunization. In the future, FNAIT may be managed similar to HDN 

although immunization in early pregnancy cannot be prevented by prophylaxis. 

Source: EMBASE 

2. Early relapse of thrombotic thrombocytopenic purpura(TTP)/hemolytic uremic 

syndrome (HUS) refractory to plasma exchange associated with catheter related 

acinetobacter baumannii bacteremia 

Author(s): Chang J.W., Tsai C.S., Lin T.H., Hsieh H.H., Tsai Y.U., Lu K.M. 

Citation: Vox Sanguinis, December 2011, vol./is. 101/(117-118), 0042-9007 (December 

2011) 


Abstract: Abstract: Thrombotic thrombocytopenic purpura (TTP)/Hemolytic-uremic 

syndrome (HUS) is a syndrome characterized by thrombocytopenia, microangiopathic 

hemolytic anemia, fever, neurologic manifestation and renal failure. Most of the cases are 

idiopathic. Plasma exchange is one of the standard treatment for TTP/HUS. However, 

secondary TTP/HUS associated with bacterial, viral and mycobacterial infections, drugs, 

autoimmune disease, pregnancy, solid tumors and bone marrow transplantation have 

been described. Early relapse associated with catheter-related bacteremia is a rare 

occurrence. The patient we report had a classic presentation of TTP/HUS that responded 

to plasma exchange but relapsed earlier as reflected by the increased schistocytosis, 

decreased hematocrit, decreased platelet counts and increased lactate dehydrogenase. 

This relapse may be attributed to Acinetobacter baumannii bacteremia, secondary to 

chemo-port infection. After removal of the chemo-port, the syndromes of TTP/HUS had 

improved without additional plasma exchange. The importance of identifying the possible 

bacterial colonization of an indwelling catheter is thus emphasized. 


3. Thrombocytopenia in a girl with idiopathic central precocious puberty treated with 

longterm gonadotropin hormone agonists (GnRHa) 

Author(s): Krstevska-Konstantinova M., Janchevska A., Gucev Z. 

Citation: Hormone Research in Paediatrics, October 2011, vol./is. 76/(268), 1663-2818 

(October 2011) 


Abstract: Background: Central precocious puberty (CPP) is a frequent endocrine problem 

in childhood. The idiopathic and organic etiology of CPP are most commonly treated with 

GnRH agonists. They have been considered in many studies to be safe and effective. Case 

report: We present a 7 year old girl with idiopathic CPP diagnosed by standard GnRH 

testing. She developed severe thrombocitopenia during GnRH treatment. The familial 

history showed that the mother has been treated 8 years for infertility. The pregnancy 

was controlled and uneventful. At the time of diagnosis her weight was at the 75th 

percentile and she was 130.5 cm tall on the 97th percentile. The Tanner stage was B3, A1, 

P1. The bone age was advanced to 8.5 years. Before the treatment she was otherwise 

healthy. All laboratory evaluations were normal from blood count to thyroid function and 

brain imaging thehnicques. After receiving her 9th monthly depot therapy of GnRH 

55

agonist, triptorelin acetate, 3,75 mg i.m., she developed bleeding from the injection site, 

bruises and rush on the skin all over her body. Her platelets were 27 x 10 3 /mul (150-300 x 

10 3 /mul). The coagulation factors and myelogram were normal. She was hospitalized at 

the haematology department in our hospital for 5 days and treated with corticosteroids. 

Recovery was after one week and treatment with GnRH agonists was discontinued. 

Conclusions: To our knowledge, thrombocitopenia has not been yet reported in children 

receiving GnRH agonist treatment. This may represent a possible serious adverse effect 

which needs further investigation. 


4. Successful rituximab treatment of refractory immune thrombocytopenia during 

pregnancy 

Author(s): Schmid J., Piroth D., Buhrlen M., Maass N., Brummendorf T.H., Galm O. 

Citation: Onkologie, September 2011, vol./is. 34/(240), 0378-584X (September 2011) 


Abstract: Immune thrombocytopenia (ITP) is mediated by autoantibodies resulting in 

accelerated platelet destruction. ITP clinically manifests in bleeding and can present with 

minor symptoms as petechiae, but may also lead to severe intracranial hemorrhage. ITP 

with severe thrombocytopenia < 50.000/microL may occur in women during pregnancy 

representing a challenge in terms of management and treatment. If corticosteroids and 

IVIG (intravenous immungloblin) are not successful, administration of rituximab may be 

considered. However, since the IgG-antibody rituximab potentially crosses the placenta, 

binding to fetal peripheral B-lymphocytes may subsequently cause immunosuppression. 

The following case report describes the effects of rituximab given to a pregnant woman 

with ITP after corticosteroids and IVIG had failed to durably increase the platelet count. 

Furthermore, reduction of corticosteroids was necessary owing to fetal macrosomy. 

Rituximab treatment was initiated in the 25th week of pregnancy and was given weekly 

four times (375 mg/m2) leading to a transient increase in maternal platelet count. There 

occurred no bleeding complications during and after primary cesarean section. In the 

mother platelet count was already normalized three days post partum. In the neonate, 

rituximab caused complete B-lymphocyte depletion. B-lymphocyte count was normalized 

at two months after delivery, whereas immunoglobulin levels were still inadequate at the 

age of 11 months. However, there occurred no complications related to infection in the 

neonate. The clinical course indicates that rituximab treatment during pregnancy is 

feasible. Administration of rituximab during pregnancy should be carefully considered for 

selected cases. 


5. Acute kidney injury in pregnancy: The thrombotic microangiopathies 

Author(s): Ganesan C., Maynard S.E. 

Citation: Journal of Nephrology, September 2011, vol./is. 24/5(554-563), 1121-8428;1724- 

6059 (September-Octember 2011) 


Abstract: Acute kidney injury (AKI) is a rare but serious complication of pregnancy. 

Although prerenal and ischemic causes of AKI are most common, renal insufficiency can 

complicate several other pregnancy-specific conditions. In particular, severe 

preeclampsia/HELLP syndrome, acute fatty liver of pregnancy (AFLP) and thrombotic 

thrombocytopenic purpura (TTP) are all frequently complicated by AKI, and share several 

clinical features which pose diagnostic challenges to the clinician. In this article, we discuss 

the clinical and laboratory features, pathophysiology and treatment of these 3 conditions, 

56

with particular attention to renal manifestations. It is imperative to distinguish these 

conditions to make appropriate therapeutic decisions which can be lifesaving for the 

mother and fetus. Typically AFLP and HELLP improve after delivery of the fetus, whereas 

plasma exchange is the first-line treatment for TTP. 


Full Text: 


6. Thrombotic thrombocytopenic purpura: Overview on the last 10 years of plasma 

exchange treatment in hospital So Jose, Lisbon 

Author(s): Santos A., Guttierrez M.J., Tavares M.L. 

Citation: Vox Sanguinis, July 2011, vol./is. 101/(296), 0042-9007 (July 2011) 


Abstract: Introduction Thrombotic Thrombocytopenic Purpura (TTP) was first described by 

Moschowitz in 1924. It is a rare disease. In the era before therapeutic plasma exchange 

(PE) 90% of patients died from systemic microvascular thrombosis. PE removes the 

causative antibody to von Willebrand factor cleaving metalloprotease (ADAMTS13) and 

replaces it. Recognition of TTP can be difficult because of the variety of presentations and 

lack of specific diagnosis criteria. A diagnosis of TTP may be made in the presence of a 

microangiopathic haemolytic anaemia and thrombocytopenia in the absence of any other 

identifiable cause. Material and methods: Patient's Hospital medical records were 

reviewed since January 2000 until December 2010. Results: In the last ten years we 

performed PE in fourteen adult patients (eleven females and three males). Twenty-one 

episodes of TTP were observed: one was related to HIV infection and four were related 

with first trimester pregnancy. Clinical presentation was heterogeneous and differential 

diagnosis was almost exclusively made with acute leukaemia. The most frequent symptom 

was mucocutaneous bleeding. Daily PE with replacement of 1.0 to 1.5 times the predicted 

plasma volume of the patient was performed, for a minimum of two days after platelet 

count and lactate desidrogenase returned to normal. CobeSpectra (Caridian) was used; 

the replacement fluid administrated was solvent/detergent-treated plasma (Octaplas, 

Octapharma); central venous access was used in all patients. Adjuvant corticosteroid 

therapy was instituted. PE was effective in all but one episode. Four patients relapsed. 

Four patients were submitted to immunosuppressive agents (rituximab, azatioprin and 

cyclophosphamid) when exacerbations or relapse occurred. No measurements of 

ADAMTS13 activity or antibody were made. Complications associated with PE were minor 

(allergic reaction and high blood pressure). Conclusions: PE is the only treatment for which 

there are firm data on its effectiveness in TTP in adults. A high index of suspicion is 

required for rapid diagnosis and prompt initiation of PE treatment. PE should be instituted 

within 24 hours of presentation of TTP. Plasma infusion remains appropriate when there 

may be a delay until PE is available. The optimal duration of therapy is unknown and once 

a patient is in remission the efficacy of any treatment to prevent relapses is uncertain. 


7. Towards immunological understanding of foetal/neonatal alloimmune 

thrombocytopenia based on a study of more than 100,000 pregnancies? 

Author(s): Husebekk A., Skogen B., Ahlen M.T., Eksteen M., Heide G., Killie M.K., Killie 

I.M.L., Kjeldsen-Kragh J., Ni H., Stuge T. 



57

Abstract: Background: The most common immune responses in transfusion medicine and 

in incompatible pregnancies are immune responses to the RhD antigen on red cells, HLA 

class I molecules on white cells and platelets, and human platelet antigens. The structure 

of these antigens is different; more than 30 epitopes have been detected on the RhD 

antigens, HLA antigens are highly polymorphic and induce strong alloimmune responses 

whereas the HPA antigens are created by one amino acid difference in allotypes based on 

a single nucleotide polymorphism at the genetic level. In Caucasians, HPA-1a induces 

immune response and antibody production in 10% of HPA 1b homozygous women in 

connection with an HPA-1 incompatible pregnancy. Maternal anti-HPA-1a antibodies of 

IgG class cross placenta, bind to foetal HPA-1a positive platelets which are phagocytosed. 

The thrombocytopenia renders the foetus/newborn at risk of haemorrhage. Data from 

screening of more than 100,000 pregnancies made it possible to understand the biology of 

FNAIT in more detail. Aim: The aim of the study was to understand the mechanism of 

HPA-1a immunisation and to propose methods for prevention of immunisation and 

treatment of women who are already immunised. Methods: Both T cells, B cells and anti- 

HPA-1a antibodies were isolated from HPA-1a alloimmunised women. HPA-1a specific T 

cells were isolated after sorting and stimulation with relevant antigen, presented by cells 

with HLA DRB30101 HLA class II molecules. Monoclonal anti-HPA-1a IgG was generated by 

immortalization of memory B cells. The IgG fraction was isolated from plasma from 

women with high level of anti-HPA-1a antibodies. The anti-HPA-1a-mediated immune 

suppression was studied in a murine FNAIT model. Results: Analysis of 100,448 

pregnancies showed that 2.1% of the pregnant women were homozygous HPA 1bb and 

10.6% had detectable antibodies after HPA 1 incompatible pregnancies. It was also shown 

that approximately 25% of the women were immunised during the first incompatible 

pregnancy and 75% in connection with delivery. Alloimmunised women with blood group 

A gave birth to babies with the most severe thrombocytopenia. Both HPA-1a specific 

clonal T cells and B cells were isolated from immunized women. The clonal T cells could be 

stimulated both by peptides and native antigens provided HLA DRB30101 positive antigen 

presenting cells. Studies in mice showed that antibody mediated immune suppression 

(AMIS) could be induced and clinical complications prevented if platelet specific 

antibodies were injected in connection with immunisation. Summary/conclusions: The 

study shows that the pathophysiology of FNAIT and haemolytic disease of the newborn 

(HDN) are more similar than believed so far. In HPA 1bb, HLA DRB30101 women with 

blood group A, the anti-HPA-1a antibodies induce more severe thrombocytopenia in the 

babies compared with mothers with other blood types. The level of maternal antibodies 

correlates with the severity of thrombocytopenia in the newborn. There is evidence, in 

murine studies, for an AMIS effect of anti-HPA-1a antibodies injected at the time of 

immunisation which means that a prophylactic approach may be efficient in preventing 

immunisation. 


8. New insights in fetal and neonatal alloimmune thrombocytopenia 

Author(s): Cecile K., Gerald B. 

Citation: Vox Sanguinis, July 2011, vol./is. 101/(35-37), 0042-9007 (July 2011) 


Abstract: During the recent years considerable advances in the clinical and laboratory 

diagnosis of alloimmune thrombocytopenia have been done. Feto-maternal 

alloimmunization is the commonest cause of cause of severe isolated fetal and neonatal 

thrombocytopenia. The condition results from maternal immunization against specific 

fetal platelet antigens (HPA). Unlike the hemolytic disease of the fetus and newborn the 

first newborn was found to be affected. The diagnosis is usually made at birth when an 

otherwise well term infant exhibits bleeding at delivery or few hours afterwards. The most 

58

feared complication of this disorder is the occurrence of intracranial hemorrhage (ICH) as 

a result of severe thrombocytopenia leading to death or neurological sequelae. The 

diagnosis of alloimmune thrombocytopenia enables appropriate management of the 

index case and future pregnancies. The diagnosis is confirmed by laboratory testing with 

identification of the maternal alloantibody and the offending antigen present in the fetus 

or neonate that is absent in the mother. In a recent retrospective study concerning 75 

HPA-1b1b women we have shown that the diagnosis of maternal alloimmunization was 

mostly established at delivery and the women were primigravida in 51% of the cases. The 

deleterious consequence of this severity was evidenced by in utero or post-natal ICH. 

Subsequent pregnancies were managed according to three different protocols, steroids 

only, IVIG or IVIG and steroids. We have found that the most efficacious antenatal therapy 

for fetal alloimmune thrombocytopenia is maternal treatment with IVIG and steroids. In 

summary, this study shows (1) that the morbidity linked with this condition is important to 

be considered for further antenatal screening (2) that antenatal management in referral 

centers should be suggested to high-risk pregnant women. Introduction: Fetal and 

neonatal alloimmune thrombocytopenia (FNAIT) resulting from maternal immunization 

against specific fetal platelet antigen [1] affects the fetus early during pregnancy[2]. This 

syndrome as been considered as the platelet counterpart of hemolytic disease of the 

neonate (HDN) but in contrast to HDN, retrospective studies have shown that the first 

pregnancy was frequently affected[3]. The fetus has long been considered as an innocent 

bystander. However recent studies in a Mouse model have shown that the fetal major 

histocompatibility complex class I related neonatal Fc receptor (FcRn) is implicated in the 

transfer of maternal alloantibodies[4]. FNAIT is the most common cause of severe isolated 

fetal/neonatal thrombocytopenia, which the most feared complication is the occurrence 

of intracranial hemorrhage (ICH) leading to death or neurological sequelae. The incidence 

of FNAIT has been estimated to 1/800 to 1/1000 live births in Caucasians. However 

because of the absence of clinical bleeding in moderate thrombocytopenia, these cases 

would be overlooked in the absence performing routine screening. Clinical presentation: 

Fetal thrombocytopenia has been defined in as a platelet count less than 150x10 9 /L, 

irrespective of the gestational age[5]. Fetal thrombocytopenia is often discovered when 

ICH has occurred. Sonography reveals ventriculomegaly or fetal hydrocephalus. ICH has 

been documented whatever the implicated platelet alloantigens, (25.5% of cases for HPA- 

1a, 24% for HPA-3a, 15% for HPA-5b)[6], leading to death in up to 10% or neurological 

sequelae in up to 20% of the reported cases. In a literature review it has been reported 

that 80% of ICH occur in utero and 40% are diagnosed before 30 weeks of gestation[6]. 

Most commonly, neonatal thrombocytopenia is suspected in otherwise well term infant 

with unexplained bruising and purpura. In some circumstances, severe bleeding as ICH, 

large cephalohematoma, gastrointestinal or genitourinary hemorrhage is observed. In any 

case a platelet count should be obtained. The risk of life-threatening hemorrhage in case 

of severe thrombocytopenia necessitates prompt diagnosis and therapy. Conversely the 

infant may be symptomless with thrombocytopenia discovered incidentally when a blood 

count is obtained for another reason i.e. to exclude sepsis. Our recent retrospective study 

shows that the diagnosis of maternal platelet alloimmunization in our cohort was 

established either during the pregnancy (9 women) or at delivery (66 women)[7]. In this 

series the pregnant women were primigravida in 51% of the cases. The cases referred to 

the laboratory for investigation were severe with 6 ICH detected antenatally while three 

cases were diagnosed in the post-natal period, leading to death for two neonates. The 

severe thrombocytopenia in our index cases (80% of the neonates with a platelet count 

below 50 x10 9 /L) was not correlated either with the maternal alloantibody concentration 

at delivery, or the maternal genetic background (ABO or HLA). It is important to point out 

that eight neonates were born before the diagnosis of FNAIT: six infants had no medical 

problem despite the HPA-1 feto-maternal incompatibility (no platelet count performed at 

the time), and two were thrombocytopenic but the FNAIT diagnosis was not done at the 

time. Therefore, unexpected or unexplained neonatal thrombocytopenia or severe early- 

59

onset thrombocytopenia should raise the possibility of FNAIT and guide investigations 

accordingly. Laboratory testing for suspected FNAIT: The diagnosis of FNAIT is important: 

(1) for the management of the index case, and (2) for the antenatal management of 

subsequent pregnancies. The laboratory diagnosis relies on the detection and 

identification of the maternal antiplatelet antibody, and identification of the offending 

antigen. Investigation should be performed by an experienced laboratory that has the 

ability to perform antigencapture assays for antibody testing, and typing of common 

HPAs, and even rare or new platelet alloantigens. To date, 27 platelet-specific alloantigens 

have been described, 12 with a bi-allelic polymorphism[8] (http://www. 

ebi.ac.uk/ipd/hpa/). Frequencies of platelet antigens vary among different populations. In 

Caucasians, HPA-1a is by far the most common antigen implicated in FNAIT, followed at 

much lower frequency by HPA-5b, then HPA-3. In contrast, in Asians, FNAIT is essentially 

linked with HPA-4 and HPA-5b. During recent years FNAIT has been reported involving 

rare or private antigens, most of them located on the GPIIb-IIIa complex. The description 

of such antigens has been possible with the introduction of a routine maternal-paternal 

cross-matching with an antigen-capture assay and a panel of mouse monoclonal 

antibodies in investigations of suspected cases of FNAIT. Recent studies have shown these 

low-frequency antigens being not restricted to single families [9-11]. Detection and 

identification of the causative maternal alloantibody is done by an Elisa antigen-capture 

assay, and the MAIPA (Monoclonal Antibody-specific Immobilization of Platelet Antigens 

[12]) is considered the gold standard reference method in platelet immunology. Platelet 

phenotyping may be performed with the MAIPA technique, although due to shortage of 

serological reagents and advance in molecular biology, platelet genotyping is usually done. 

The recent development of high-throughput technologies allows simultaneous genotyping 

of as many as 17 HPAs. However genotype is not phenotype. Discrepancies due to 

unknown mutations may alter the technique and may be responsible for false typing 

assignation with potential consequences on diagnosis and therapy [11,13]. For that reason 

we recommend the use of both phenotyping and genotyping for at least the most 

frequently involved platelet antigens. Post-natal management: Severely affected infants 

with bleeding or a platelet count 50x10 9 /L) has been reached and no additional therapy is required. Ultrasound 

examination is recommended to exclude ICH. The neonatal outcome in the absence of 

bleeding is generally favorable; a normal platelet count is obtained within a week of life. 

Antenatal management: As the severity of thrombocytopenia usually increases in 

subsequent pregnancies, antenatal management of high-risk pregnancies has been 

developed to prevent the morbidity and mortality of this condition. 


9. Maternal antibody titration as a predictive parameter for fetal status and therapy 

effectiveness in pregnancies associated with alloimmune thrombocytopenia 

Author(s): Gerald B., Cecile K. 

Citation: Vox Sanguinis, July 2011, vol./is. 101/(34-35), 0042-9007 (July 2011) 


Abstract: Alloimmune thrombocytopenia is the most common cause of severe isolated 

fetal and neonatal thrombocytopenia. In view of the recurrence of thrombocytopenia in 

subsequent pregnancies with incompatible foetuses, antenatal management has been 

developed. Until recently the only possibility of assessing the fetal status both before and 

60

during therapy was to perform fetal blood samplings (FBS). In view of the risks involved in 

the procedure, FBS has been restricted and non-invasive strategies have been developed. 

The determination of maternal parameters predictive of severe fetal thrombocytopenia is 

crucial for tailored intervention. A first retrospective study was designed to analyse the 

predictive value of the maternal anti HPA-1a antibody concentration. With this in view, we 

developed a quantitative method based on the Monoclonal Antibodyspecific 

Immobilization of Platelet Antigens (MAIPA) technique, which is the gold standard method 

for serological investigations in platelet immunology (Bertrand et al., Transfusion, 2005). 

Maternal anti HPA-1a antibody concentrations were determined at the same time as the 

FBS carried out as a part of the antenatal management prior to therapy. A statistically 

significant correlation was observed between the high antibody concentration [>=28 

International Units (IU) /mL] and severe fetal thrombocytopenia (50x10 9 /L; P = 0.0153; Bertrand et al. Blood, in press). In conclusion, our work gives new 

insights into maternal predictive parameters for fetal status and therapy effectiveness, 

allowing noninvasive strategies. Follow-up of the antibody concentration during 

pregnancy could help to predict the outcome of the pregnancy, so as to prevent severe 

hemorrhagic disorders in the neonate. Introduction: Alloimmune thrombocytopenia is the 

most common cause of severe isolated fetal and neonatal thrombocytopenia. This results 

from maternal immunization against fetal platelet-specific antigens inherited from the 

father. The frequency of fetal/neonatal alloimmune thrombocytopenia (F/NAIT) is about 

1/1000 live births. In Caucasian populations, incompatibility concerning the HPA-1a 

antigen plays a major role in F/ NAIT. As the severity of thrombocytopenia usually 

increases in subsequent pregnancies, antenatal management of high-risk pregnancies is 

very important in preventing the morbidity or mortality linked with severe fetal 

thrombocytopenia. Until recently the only possibility of assessing the fetal status both 

before and during therapy was to perform fetal blood samplings (FBS). In view of the risks 

involved in the procedure, FBS has been restricted and non-invasive strategies have been 

developed. The determination of maternal parameters predictive of severe fetal 

thrombocytopenia is crucial for tailored intervention. For this purpose, we designed a first 

retrospective study to analyse the predictive value of the maternal anti HPA-1a antibody 

concentration during and after pregnancy. A larger retrospective study was subsequently 

performed to search for additional maternal predictive parameters during managed 

pregnancies, taking into account maternal anti HPA-1a antibody concentrations and 

maternal genetic background (ABO blood group and HLA-DRB3 allele). The most striking 

features of these retrospective studies are presented. Methodology for quantification of 

maternal anti HPA-1a antibodies: The Monoclonal Antibody-specific Immobilization of 

Platelet Antigens (MAIPA) assay [Kiefel, 1987 179 /id] is the gold standard for the 

detection of anti platelet antibody [Kaplan, 2007 1954 /id]. The MAIPA is an 

antigencapture assay, based on the formation of trimolecular complexes by the binding of 

specific mouse monoclonal antibodies (MoAbs) and the human antibody targeting the 

platelet membrane molecule on which the respective epitopes are located. We have 

standardized this procedure for the quantification of anti HPA-1a antibodies [Bertrand, 

2005 1767 /id]. Eight serial dilutions of a reference serum containing 100 IU/mL of anti 

HPA-1a antibodies [Allen, 2005 2075 /id] were performed to construct a standard curve 

fitting with a 4-parameter logistic regression (from 1 to 1/128; Figure 1). Test sera were 

61

also diluted from 1 to 1/128, and optical density values were used for the interpolation of 

the concentration with the standard curve corrected by the dilution factor. This procedure 

was followed to determine the concentration of sera from HPA-1bb women, in a context 

of F/NAIT. Severe fetal thrombocytopenia and the predictive value of the antibody 

concentration: Prospective studies seeking a relationship between maternal alloantibody 

concentration and the fetal status have failed to reach a consensus [Bessos, 2005 1786 

/id;Durand-Zaleski, 1996 913 /id;Jaegtvik, 2000 1429 / id;Kaplan, 1988 260 /id;Killie, 2010 

2143 /id;Kurz, 1999 1721 /id;Proulx, 1994 880 /id;Williamson, 1998 1310 /id]. These 

discrepancies may be partly explained by the size of the series, the parity of the women 

enrolled, the differences in the timing of maternal sampling, and the methodology used 

for the antibody titration. We designed a first retrospective study to determine if there is 

a relationship between the maternal anti HPA-1a antibody concentration and the fetal 

platelet count. Titrations of 31 maternal sera at different stages of pregnancy [16-37 

weeks of gestation (wg)] before any antenatal therapy were determined at the same time 

as the FBS carried out as a part of the antenatal management prior to therapy. A 

statistically significant correlation was observed between the severely thrombocytopenic 

fetuses and antibody concentrations above 28 IU/mL when measured before 28 wg and 

before any treatment (Fisher's exact test P = 0.015 [Bertrand, 2006 1849 /id]). A larger 

retrospective study was subsequently performed, including 239 pregnancies from 75 HPA- 

1bb women [Bertrand, 2011 2158 /id]. The figure 2A shows fetal platelet counts 

determined by FBS, according to the maternal antibody concentrations (x-axis). This 

enlarged cohort led to an improvement in the prediction of the fetal status (P = 0.0016), 

ROC curve in Figure 2B). Follow-up of the maternal antibody concentration during 

pregnancy, and prediction of the therapy effectiveness: A recent meta-analysis from 

Bussel et al. showed that about 20% of women delivered a severely thrombocytopenic 

newborn despite the administration of immunoglobulin G (IVIG) during managed 

pregnancy [Vinograd, 2010 2177 /id]. This percentage was calculated by taking into 

account numerous studies supporting the efficacy of IVIG-therapy. In order to prevent 

severe post-natal hemorrhagic disorders, it would be of interest to predict the outcome of 

the pregnancy. We searched for additional maternal predictive parameters indicating the 

severity of the disease, at the time of the diagnosis as well as during subsequent managed 

pregnancies (IVIG-treated mothers). We took into account the gynaecologic history of the 

women, their genetic background (ABO blood group and HLA DRB3 allele), and we 

followed the maternal antibody concentration during the pregnancy of 34 IVIG-treated 

women. In our cohort, the severity of thrombocytopenia in index cases was not correlated 

with the maternal ABO blood group (P = 0.6599) or the HLA DRB3:0101 allele (P = 0.1664). 

Management of subsequent pregnancies relies on (1) an initial determination of the 

antibody concentration before 28 wg and before treatment, to determine the severity of 

the fetal status and (2) the administration of intravenous IVIG with the follow-up of the 

antibody concentration till delivery. The pattern of the antibody concentration during 

pregnancy was variable: steadily low antibody concentration, or decreasing towards 

delivery, or increasing during the second and third trimester of pregnancy or just after 

delivery. In order to analyze these curve tendencies, we measured the area under curve 

(AUC) of each antibody follow-up (34 managed pregnancies), and weighted the AUC by 

the weeks' gestation between the first and the last quantification. Figure 3 reports an 

example of antibody follow-up during the pregnancies of two women, both pregnant for 

the second time. The antibody concentration followed during pregnancy A remained very 

low (weighted AUC = 6 IU/mL/wg) and the newborn had a normal platelet count. On the 

contrary, the antibody concentration was very high during pregnancy B (weighted AUC = 

69 IU/mL/wg), and the newborn was severely thrombocytopenic (post-natal therapy 

necessitates platelet transfusion associated with IVIG injections). Proceeding with this 

methodology for the 34 pregnancies, our study showed that this new maternal parameter 

is predictive of the therapy failure: under 28 IU/mL/wg, a majority of newborns were 

below the safe platelet count of 50x10 9 /L (P = 0.0153). 

62


10. Successful management of a planned pregnancy in severe congenital thrombotic 

thrombocytopaenic purpura: The Upshaw-Schulman syndrome 

Author(s): Richter J., Strandberg K., Lindblom A., Strevens H., Karpman D., Wide-Swensson 

D. 

Citation: Transfusion Medicine, June 2011, vol./is. 21/3(211-213), 0958-7578;1365-3148 

(June 2011) 



11. Use of fondaparinux in a pregnant woman with pulmonary embolism and heparininduced 

thrombocytopenia 

Author(s): Ciurzynski M., Jankowski K., Pietrzak B., Mazanowska N., Rzewuska E., Kowalik 

R., Pruszczyk P. 

Citation: Medical Science Monitor, May 2011, vol./is. 17/5(CS56-CS59), 1234-1010;1643- 

3750 (May 2011) 


Abstract: Background: A serious complication of heparin treatment, heparin-induced 

thrombocytopenia (HIT) is rarely observed in pregnant women. Drug therapy during 

pregnancy should always be chosen to minimize fetal risk. The management of HIT in 

pregnancy represents a medical challenge. Unlike heparins, the anticoagulants used in 

patients with HIT do cross the placenta, with unknown fetal effects. Case Report: We 

present a case of a 24-year-old female presenting for care at 34 weeks of gestation with 

acute pulmonary embolism treated initially with unfractionated heparin (UFH) and low 

molecular weight heparin (LMWH), who developed HIT. She was then successfully treated 

with fondaparinux. Conclusions: To the best of our knowledge, this is one of the first case 

reports describing a successful use of fondaparinux in the treatment of HIT in a thirdtrimester 

pregnant woman, providing a novel approach for this subset of patients. Med 

Sci Monit, 2011. 


12. Diagnosis and management of thrombocytopenia in pregnancy 

Author(s): Myers B., Truelove E. 

Citation: Fetal and Maternal Medicine Review, May 2011, vol./is. 22/2(144-167), 0965- 

5395;1469-5065 (May 2011) 


Abstract: In conclusion, there are a large number of causes of thrombocytopenia in 

pregnancy. By far the most common causes are mild, but awareness of the complex 

disorders in which thrombocytopenia occurs is essential to ensure prompt diagnosis and 

referral into a centre with expertise in these rare conditions, to optimise outcome for 

mother and baby. 2011 Cambridge University Press. 


13. The American Society of Hematology 2011 evidence-based practice guideline for 

immune thrombocytopenia 

Author(s): Neunert C., Lim W., Crowther M., Cohen A., Solberg Jr. L., Crowther M.A. 

63

Citation: Blood, April 2011, vol./is. 117/16(4190-4207), 0006-4971;1528-0020 (21 Apr 

2011) 


Abstract: Immune thrombocytopenia (ITP) is commonly encountered in clinical practice. In 

1996 the American Society of Hematology published a landmark guidance paper designed 

to assist clinicians in the management of this disorder. Since 1996 there have been 

numerous advances in the management of both adult and pediatric ITP. These changes 

mandated an update in the guidelines. This guideline uses a rigorous, evidence-based 

approach to the location, interpretation, and presentation of the available evidence. We 

have endeavored to identify, abstract, and present all available methodologically rigorous 

data informing the treatment of ITP. We provide evidence-based treatment 

recommendations using the GRADE system in those areas in which such evidence exists. 

We do not provide evidence in those areas in which evidence is lacking, or is of lower 

quality - interested readers are referred to a number of recent, consensus-based 

recommendations for expert opinion in these clinical areas. Our review identified the 

need for additional studies in many key areas of the therapy of ITP such as comparative 

studies of "front-line" therapy for ITP, the management of serious bleeding in patients 

with ITP, and studies that will provide guidance about which therapy should be used as 

salvage therapy for patients after failure of a first-line intervention. 2011 by The American 

Society of Hematology. 


Full Text: 


14. Thrombocytopenia in Pregnancy 

Author(s): Bockenstedt P.L. 

Citation: Hematology/Oncology Clinics of North America, April 2011, vol./is. 25/2(293- 

310), 0889-8588 (April 2011) 







counts less than 100,000/muL require careful hematological and obstetric consultation to 

exclude more serious disorders. 2011 Elsevier Inc. 


15. ADAMTS13 activity and the risk of thrombotic thrombocytopenic purpura relapse 

in pregnancy 

Author(s): Raman R., Yang S., Wu H.M., Cataland S.R. 

Citation: British Journal of Haematology, April 2011, vol./is. 153/2(277-279), 0007- 

1048;1365-2141 (April 2011) 



16. Fetal alloimmune thrombocytopenia: Is less invasive antenatal management safe? 

64

Author(s): Mechoulan A., Kaplan C., Muller J.Y., Branger B., Philippe H.J., Oury J.-F., Ville Y., 

Winer N. 

Citation: Journal of Maternal-Fetal and Neonatal Medicine, April 2011, vol./is. 24/4(564- 

567), 1476-7058;1476-4954 (April 2011) 


Abstract: Objectives. The aim of this study was to review recent multicenter data on 

antenatal management of anti-HPA-1a fetal alloimmune thrombocytopenia and, based on 

this retrospective study and on recent literature, to evaluate if FBS modified the 

obstetrical management. Material and methods. This retrospective study in France 

includes 23 pregnancies in 21 women who had a previous thrombocytopenic infant due to 

anti HPA-1a alloimmunization. All pregnant women received intravenous immunoglobulin 

(IVIG) treatment, with or without corticosteroids. Fetal blood sampling (FBS) was 

performed before any therapy (four cases) or during pregnancy (nine cases). Results. 

Infants whose mother received treatment had a significantly higher neonatal platelet 

count than the corresponding sibling (p = 0.003). In eight cases, therapy was started late 

during pregnancy. In three cases, treatment was discontinued 3 or 4 weeks before birth, 

and this was associated with a poorer result. No in utero intracranial hemorrhage was 

recorded in the infants for whom maternal therapy continued to term. Adverse effects 

were not observed in any case. All babies were delivered by cesarean even when FBS was 

performed. One emergency cesarean was performed for fetal bradycardia after FBS. 

Conclusion. This study confirmed that maternal therapy with intravenous immunoglobulin 

for fetal alloimmune thrombocytopenia gives satisfactory results. It also showed that a 

less invasive approach, especially a reduction in the number of fetal blood samples, is 

possible without deleterious consequences. This observation suggests also to start IVIG 

early during pregnancy and to continue treatment up to delivery. 2011 Informa UK, Ltd. 



hemodiafiltration membranes 

Author(s): Venditto M., Bourry E., Szumilak D., Deray G. 

Citation: American Journal of Kidney Diseases, March 2011, vol./is. 57/3(521), 0272-6386 

(March 2011) 



18. Prediction of the fetal status in noninvasive management of alloimmune 


Author(s): Bertrand G., Drame M., Martageix C., Kaplan C. 

Citation: Blood, March 2011, vol./is. 117/11(3209-3213), 0006-4971;1528-0020 (17 Mar 

2011) 


Abstract: Fetal/neonatal alloimmune thrombocytopenia is the most common cause of 

severe thrombocytopenia in the fetus and in an otherwise healthy newborn. To counter 

the consequences of severe fetal thrombocytopenia, antenatal therapies have been 

implemented. Predictive parameters for fetal severe thrombocytopenia are important for 

the development of noninvasive strategy and tailored intervention. We report here data 

concerning 239 pregnancies in 75 HPA-1bb women. Analysis of the index cases (diagnosis 

of fetal/neonatal alloimmune thrombocytopenia) did not show any significant correlation 

between the severity of the disease and the maternal genetic background (ABO blood 

65

group and HLA-DRB3 allele). Subsequent pregnancies were managed, and therapy 

effectiveness was evaluated. The highest mean newborn platelet count was observed for 

a combination of intravenous immunoglobulin and steroids (135 x 10 9 /L; 54 newborns) 

compared with intravenous immunoglobulin alone (89 x 10 9 /L; 27 newborns). The 

maternal anti-HPA-1a antibody concentration measured before any treatment and before 

28 weeks of gestation was predictive of the fetal status. The weighted areas under curves 

of the maternal alloantibody concentrations were predictive of therapy response. To 

conclude, this large retrospective survey gives new insights on maternal predictive 

parameters for fetal status and therapy effectiveness allowing noninvasive strategies. 

2011 by The American Society of Hematology. 


Full Text: 


19. Thrombotic thrombocytopenic purpura with complete molar pregnancy: a case 

report 

Author(s): Meng H., Kumar N.S., Nannapaneni J., Inglis S.R. 

Citation: The Journal of reproductive medicine, March 2011, vol./is. 56/3-4(169-171), 

0024-7758 (2011 Mar-Apr) 


Abstract: Thrombotic thrombocytopenic purpura (TTP) is extremely rare. This disease and 

its prompt diagnosis are important because TTP in pregnancy carries a 90% mortality rate. 

A 21-year-old woman underwent suction dilation and curettage for molar pregnancy. 

Postoperatively the patient developed severe hypertension, microangiopathic anemia, 

thrombocytopenia and chest pain associated with ischemic cardiac changes. Despite 

blood and plasma transfusions and steroid therapy, the patient continued to have 

worsening hemolysis and thrombocytopenia. TTP was diagnosed, and plasmapheresis led 

to a rapid recovery. TTP can occur with molar pregnancy. Making this diagnosis in a timely 

manner is crucial to ensure that potentially life-saving plasmapheresis is initiated in a 

timely manner. To our knowledge, this is the first reported case of thrombotic 

thrombocytopenic purpura with molar pregnancy. 



management and outcome 

Author(s): Gasim T. 

Citation: The Journal of reproductive medicine, March 2011, vol./is. 56/3-4(163-168), 

0024-7758 (2011 Mar-Apr) 


Abstract: To evaluate the complications of pregnancy and perinatal outcome in women 

with idiopathic thrombocytopenic purpura (ITP). A retrospective analysis of 38 singleton 

pregnancies, their course, obstetric management and perinatal outcome of 32 patients 

with known ITP was undertaken. No major antenatal complications were noted among the 

patients. There were no maternal deaths, and only 1 stillbirth occurred in the series. 

Fourteen infants were delivered by cesarean section and 24 by vaginal delivery. Neonatal 

cord blood platelet count was performed in each of the live-born infants and revealed 

thrombocytopenia in 16 infants, but in only 6 (16.2%) of them was the cord blood platelet 

count < 50 x 10(9)/L. There was no neonatal death in the study, although 6 infants 

required supportive treatment with corticosteroids and intravenous immunoglobulin G. 

66

No maternal features could be used to predict the neonatal platelet count at birth. These 

results are comparable with other studies in the recent literature. Due to the low 

incidence of poor neonatal outcome in mothers with ITP, obstetric intervention based 

solely on their platelet count is not justified. Every patient with ITP should be managed 

individually, and the routine use of cesarean section should be abandoned. 


21. Delayed heparin-induced thrombocytopenia in pregnant patient with APLA: 

Diagnosis and treatment 

Author(s): Kozak N., Sigler E., Fleisher S., Tomer A. 

Citation: Thrombosis Research, February 2011, vol./is. 127/(S134), 0049-3848 (February 

2011) 


Abstract: A 26 y/o patient was diagnosed with APLA syndrome after her first unprovoked 

DVT. The laboratory data confirmed the triple positivity, i.e., strongly positive LAC, and 

high titers (more than 100) both of anticardiolipin and anti-beta2glycoprotein. The patient 

was placed on Warfarin and two months later after becoming pregnant she switched to 

therapeutic LMWH. The pregnancy was uneventful up to 32 week when sudden drop in 

platelet count (from 287x10 3 to 70x10 3 in a week) raised the suspicion of HIT in spite of 

unusual timing and context. PaGIA test was positive but considering possible cross 

reactivity with APLA we decided to perform the confirmatory functional flow cytometric 

assay (FCA) which determines the capacity of the patient's serum to activate platelets in 

the presence of Heparin. FCA was also positive. LMWH was stopped and the patient was 

placed on Fondaparinux with gradual improvement in platelet count after 4 days of 

treatment. She continued on this regimen until regular vaginal delivery when her platelets 

were 110x10 3 . Five days after delivery additional increase up to 210x10 3 enabled her to 

restart Warfarin. This case presents a number of special features: successful pregnancy 

with very high APLA titers, HIT in pregnancy and after six months of treatment, 

combination of HIT and APLA. In addition of note is the application of flow cytometry as 

confirmatory diagnostic assay and use of Fondaparinux in HIT in pregnancy with good 

results and without any complications. 


22. Unusual case of thrombocytopenia with terminal 1Q deletion 

Author(s): Syed S.A., Martinez J., Savells K. 

Citation: Journal of Investigative Medicine, February 2011, vol./is. 59/2(448), 1081-5589 

(February 2011) 


Abstract: Case Report: Introduction: Terminal deletion of chromosome 1q is a 

recognizable entity usually presenting with abnormalities of the CNS and skeletal system. 

Hematological abnormalities are however rare. We present the first reported case of 1q 

terminal deletion with persistent neonatal thrombocytopenia. A male infant was born via 

C-section secondary to multiple fetal anomalies, at 36 weeks gestation to a 

nonconsanguineous couple. The pregnancy was complicated by abnormal prenatal 

ultrasound that showed polyhydramnios, micrognathia, and a 2 vessel cord. At birth, the 

infant was noted to be pale with poor perfusion. Birth weight was 2295grams (10th %), 

length 44.5cm (10th %), head cir. 31.5 cm (10th %). Multiple anomalies were present at 

birth including short neck, low set dysplastic ears, short upturned nose, micrognathia, 

micro-penis with hypospadias, hypoplastic and empty scrotum, puffy hands and digits, 

flexion contracture, (claw hands). ECHO showed ventriculoseptal defect (VSD) and large 

67

atrial septal defect. Cranial Doppler showed agenesis of the corpus callosum, hypoplastic 

cerebellar vermis, and large ventricles communicating with normal-size cisterna magna. 

Abdominal ultrasound showed mild bilateral hydronephrosis and small splenic cyst. Labs 

at birth showed thrombocytopenia (platelet count of 9) and severe anemia (H/H 5.6/16). 

Over the course of NICU stay, anemia resolved after one PRBC transfusion at birth. 

However, a thrombocytopenia persisted that required multiple platelet transfusions. 

Secondary to good response to platelet transfusion, his problem seems to be related to 

platelet production rather than destruction therefore related to a dysplastic bone marrow 

function. The infant failed a hearing screen in both ears. Both CMV and toxoplasmosis 

were negative. CGH array revealed del (1)(q42.3 or 43->qter) and a dup(2)(q37.3->qter). 

Conclusion: The baby was born with most of the clinical features of deletion 1q42 

including agenesis of corpus callosum, hypospadias, cardiovascular anomalies, and other 

less common manifestations including Cutis marmorata and claw-shaped hands. 

Thrombocytopenia has not been previously reported in patients with this deletion which 

made our case an unusual one. 


23. Thrombocytopenia and disorders of platelet function in pregnancy 

Author(s): Kadir R.A., McLintock C. 

Citation: Seminars in Thrombosis and Hemostasis, 2011, vol./is. 37/6(640-652), 0094- 

6176;1098-9064 (2011) 


Abstract: Pregnancy is associated with physiological and pathological changes in platelet 

numbers and function, which can be of clinical concern because of risks for maternal and 

fetal or neonatal bleeding. Thrombocytopenia in pregnancy is frequently encountered and 

may be due to increased platelet turnover and plasma dilution, immune-mediated 

mechanisms, or a complication of a more severe underlying pregnancy-related disorder 

such as preeclampsia. Inherited defects in platelet function and number may also manifest 

during pregnancy with the risk of bleeding dependent on the underlying problem. In some 

women, the diagnosis of thrombocytopenia will precede pregnancy but in others, the 

problem is first identified when routine pregnancy blood tests are performed. An accurate 

diagnosis and risk assessment in the antenatal period are essential for developing specific 

plans for any antenatal interventions and for management of delivery and the postpartum 

periods, and the neonate. Management of pregnant women with platelet disorders 

requires a multidisciplinary approach and close collaboration between the obstetric and 

hematology teams. 2011 by Thieme Medical Publishers, Inc. 


24. Antenatal interventions for fetomaternal alloimmune thrombocytopenia 

Author(s): Rayment R., Brunskill S.J., Soothill P.W., Roberts D.J., Bussel J.B., Murphy M.F. 

Citation: Cochrane database of systematic reviews (Online), 2011, vol./is. 5/(CD004226), 

1469-493X (2011) 


Abstract: Fetomaternal alloimmune thrombocytopenia results from the formation of 

antibodies by the mother which are directed against a fetal platelet alloantigen inherited 

from the father. The resulting fetal thrombocytopenia (reduced platelet numbers) may 

cause bleeding, particularly into the brain, before or shortly after birth. Antenatal 

treatment of fetomaternal alloimmune thrombocytopenia includes the administration of 

intravenous immunoglobulin (IVIG) and/or corticosteroids to the mother to prevent 

severe fetal thrombocytopenia. IVIG and corticosteroids both have short-term and 

68

possibly long-term side effects. IVIG is also costly and optimal regimens need to be 

identified. To determine the optimal antenatal treatment of fetomaternal alloimmune 

thrombocytopenia to prevent fetal and neonatal haemorrhage and death. We searched 

the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2011) and 

bibliographies of relevant publications and review articles. Randomised controlled studies 

comparing any intervention with no treatment, or comparing any two interventions. Two 

review authors independently assessed eligibility, trial quality and extracted data. We 

included four trials involving 206 people. One trial involving 39 people compared a 

corticosteroid (prednisone) versus IVIG alone. In this trial, where analysable data were 

available, there was no statistically significant differences between the treatment arms for 

predefined outcomes. Three trials involving 167 people compared IVIG plus a 

corticosteroid (prednisone in two trials and dexamethasone in one trial) versus IVIG alone. 

In these trials there was no statistically significant difference in the findings between the 

treatment arms for predefined outcomes (intracranial haemorrhage; platelet count at 

birth and preterm birth). Lack of complete data sets and important differences in 

interventions precluded the pooling of data from these trials. The optimal management of 

fetomaternal alloimmune thrombocytopenia remains unclear. Lack of complete data sets 

for two trials and differences in interventions precluded the pooling of data from these 

trials which may have enabled a more developed analysis of the trial findings. Further 

trials would be required to determine optimal treatment (the specific medication and its 

dose and schedule). Such studies should include long-term follow up of all children and 

mothers. 


Full Text: 


25. IVIG to prevent fetal intracranial hemorrhage in fetal and neonatal alloimmune 

thrombocytopenia (FNAIT): Can we reduce the dose to 0.5 g/kg/wk? 

Author(s): Wikman A., Tiblad E., Westgren M., Paridaans N., Kamphuis M., Lopriore E., 

Oepkes D., Van Den Akker E. 

Citation: American Journal of Obstetrics and Gynecology, January 2011, vol./is. 204/1 

SUPPL.(S32-S33), 0002-9378 (January 2011) 


Abstract: OBJECTIVE: The standard and highly effective treatment of pregnancies with 

FNAIT in which the previous affected child had severe thrombocytopenia but no 

intracranial hemorrhage (ICH) is weekly intravenous administration of immunoglobulins 

(IVIG) in a dose of 1 g/kg maternal weight. IVIG is an expensive human multidonor 

bloodproduct with headaches as main clinical side-effect. Dose-finding studies were never 

performed, this dose was based on use of IVIG for other diseases. In vitro studies 

suggested that a lower dose could be just as effective. Aim of our study was to compare 

the effect of a weekly dose IVIG of 0.5 g/kg with the traditional 1 g/kg. STUDY DESIGN: 

International prospective multicenter study from the Huddinge Hospital, Karolinska 

Institute, Stockholm, Sweden and The Leiden University Medical Center, The Netherlands. 

Pregnant women with HPA-1a or 5b alloantibodies against fetal platelets, a fetus positive 

for the antigen and an affected sib without ICH were, after a successful pilot study, 

treated with 0.5 g/kg IVIG starting at 28 wks gestation. The control group consisted of 

women with FNAIT treated with 1.0 g/kg, matched for gravidity and platelet count in the 

affected sib. Primary outcome variables were occurrence of ICH and platelet count in cord 

blood at birth. RESULTS: A total of 62 pregnancies were included, 31 in each group. Fetal 

blood sampling was not done in any patient. None of the 62 neonates had ICH on cranial 

ultrasound. Mean platelet count in the affected sibs was 16x109/l (range 4-44) in the low 

69

dose group and 12x 10 9 /l(range 2-49) in the standard dose group. Mean newborn platelet 

counts in the treated patients was 113x 10 9 /l (8-267) in the low dose group versus 110x 

10 9 /l (11-279) (p=NS) in the 1 g/kg group, with 1 resp. 2 neonates with a platelet count < 

30x 10 9 /l (p=NS). CONCLUSIONS: In pregnancies with FNAIT with a previous affected child 

without ICH, IVIG in a weekly dose of 0.5 g/kg maternal weight appears to be as effective 

as the commonly used 1 g/kg. 


26. Prevention of venous thromboembolism in medical patients with 

thrombocytopenia or with platelet dysfunction: A review of the literature 

Author(s): Tufano A., Guida A., Dario Di Minno M.N., Prisco D., Cerbone A.M., Di Minno G. 

Citation: Seminars in Thrombosis and Hemostasis, 2011, vol./is. 37/3(267-274), 0094- 

6176;1098-9064 (2011) 


Abstract: Current guidelines for venous thromboembolism (VTE) primary prophylaxis are 

based on randomized clinical trials that exclude subjects at a potentially high bleeding risk. 

Thus no specific recommendation/algorithm for pharmacological prophylaxis in patients 

with thrombocytopenia and/or platelet dysfunction is available. Because at least 25% of 

subjects admitted to medical departments exhibit these conditions, information on this 

subject is provided here to optimize their VTE prophylaxis. Low platelet number/function 

and clotting abnormalities are common in patients with liver cirrhosis. However, these 

patients have a high incidence of portal and idiopathic venous thromboses, implying that 

cirrhotic coagulopathy does not protect against thrombosis. At variance with severe 

thrombocytopenia (< 50,000/muL), mild/moderate thrombocytopenia (> 50,000/muL) 

should not interfere with VTE prevention decisions. In severe thrombocytopenia, 

prophylaxis should be considered on an individual basis, however. In patients with 

antiphospholipid antibodies and thrombocytopenia, a thrombotic tendency is usually 

associated rather than a bleeding risk. VTE prophylaxis in high-risk conditions is thus 

suggested in these patients. Except in cases with contraindications to anticoagulation, 

antithrombotic prophylaxis should be always considered in hospitalized cancer patients 

with thrombocytopenia, especially in those with hematologic malignancies and multiple 

VTE risk factors. Aspirin treatment is not as effective as heparins in lowering the risk of 

VTE. Studies in stroke suggest that thromboprophylaxis with heparins is safe in patients 

with ischemic stroke undergoing aspirin treatment. The need for VTE prophylaxis in 

patients on chronic treatment with aspirin and/or clopidogrel should be evaluated after 

assessing the individual risk-benefit ratio. Copyright 2011 by Thieme Medical Publishers, 

Inc. 


27. Rituximab for management of refractory pregnancy-associated immune 

thrombocytopenic purpura 

Author(s): Gall B., Yee A., Berry B., Birchman D., Hayashi A., Dansereau J., Hart J. 

Citation: Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et 

gynecologie du Canada : JOGC, December 2010, vol./is. 32/12(1167-1171), 1701-2163 

(Dec 2010) 


Abstract: Rituximab is a novel therapy for immune thrombocytopenic purpura (ITP); 

however, information about its safety in pregnancy is limited. This case illustrates the 

successful use of rituximab to treat pregnancy-associated ITP. A 34-year-old woman 

presented with severe ITP at 23 weeks' gestation. Standard treatment with 

70

corticosteroids, intravenous immune globulin, and splenectomy failed to raise the platelet 

count. Due to ongoing bleeding, rituximab was given in the 26th week of pregnancy. The 

platelet count rose to over 100 x 10(9)/L after four weeks. The neonatal B-lymphocyte 

count normalized at four months after delivery. There were no neonatal complications of 

rituximab therapy. Rituximab may be safe for use in treating pregnancy-associated ITP. 

This case highlights the need to investigate further the safety and efficacy of rituximab in 

pregnancy. 


28. Established venous thromboembolism therapies: Heparin, low molecular weight 

heparins, and vitamin K antagonists, with a discussion of heparin-induced 


Author(s): Pendleton R.C., Rodgers G.M., Hull R.D. 

Citation: Clinics in Chest Medicine, December 2010, vol./is. 31/4(691-706), 0272-5231 

(December 2010) 
















thrombocytopenia, a prothrombotic complication of parenteral anticoagulant use. 2010 

Elsevier Inc. 


29. Different disparities of gender and race among the thrombotic thrombocytopenic 

purpura and hemolytic-uremic syndromes 

Author(s): Terrell D.R., Vesely S.K., Hovinga J.A.K., Lammle B., George J.N. 

Citation: American Journal of Hematology, November 2010, vol./is. 85/11(844-847), 0361- 

8609;1096-8652 (November 2010) 


Abstract: Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome 

(HUS) represent multiple disorders with diverse etiologies. We compared the gender and 

race of 335 patients enrolled in the Oklahoma TTP-HUS Registry across 21 years for their 

first episode of TTP or HUS to appropriate control groups. The relative frequency of 

women and white race among patients with TTP-HUS-associated with a bloody diarrhea 

prodrome and the relative frequency of women with quinine-associated TTP-HUS were 

significantly greater than their control populations. The relative frequency of women and 

black race among patients with idiopathic TTP and TTP-associated with severe ADAMTS13 

deficiency was significantly greater than their control populations. The relative frequency 

of black race among patients who had systemic lupus erythematosus (SLE) preceding TTP 

71

was significantly greater than among a population of patients with SLE, and the relative 

frequency of black race among patients with other autoimmune disorders preceding TTP 

was significantly greater than their control population. No significant gender or race 

disparities were present among patients with hematopoietic stem cell transplantationassociated 

thrombotic microangiopathy, TTP associated with pregnancy, or TTP associated 

with drugs other than quinine. The validity of these observations is supported by the 

enrollment of all consecutive patients across 21 years from a defined geographic region, 

without selection or referral bias. These observations of different gender and race 

disparities among the TTP-HUS syndromes suggest the presence of different risk factors 

and may serve as starting points for novel investigations of pathogenesis. 2010 Wiley-Liss, 

Inc. 


30. How I treat patients with thrombotic thrombocytopenic purpura: 2010 

Author(s): George J.N. 

Citation: Blood, November 2010, vol./is. 116/20(4060-4069), 0006-4971;1528-0020 (18 

Nov 2010) 


Abstract: Thrombotic thrombocytopenic purpura (TTP) is the common name for adults 

with microangiopathic hemolytic anemia, thrombocytopenia, with or without neurologic 

or renal abnormalities, and without another etiology; children without renal failure are 

also described as TTP. The diagnosis of TTP is an indication for plasma exchange 

treatment, but beginning treatment requires sufficient confidence in the diagnosis to 

justify the risk of plasma exchange complications. Documentation of a severe deficiency of 

plasma ADAMTS13 activity, defined as less than 10% of normal, is not essential for the 

diagnosis of TTP. Some patients without severe ADAMTS13 deficiency may benefit from 

plasma exchange treatment; in addition, some patients with severe ADAMTS13 deficiency 

may subsequently be diagnosed with another cause for their clinical features. However, 

severe acquired ADAMTS13 deficiency does define a subgroup of patients who appear to 

benefit from treatment with corticosteroids and other immunosuppressive agents in 

addition to plasma exchange but who have a high risk for relapse. Approximately 80% of 

patients survive their acute episode, a survival rate that has not changed since the 

introduction of plasma exchange treatment. Although recovery may appear to be 

complete, many patients have persistent minor cognitive abnormalities. More effective as 

well as safer treatment for TTP is needed. 2010 by The American Society of Hematology. 


Full Text: 


31. Successful surgical management of massive pulmonary embolism during the 

second trimester in a parturient with heparin-induced thrombocytopenia 

Author(s): Hajj-Chahine J., Jayle C., Tomasi J., Corbi P. 

Citation: Interactive Cardiovascular and Thoracic Surgery, November 2010, vol./is. 

11/5(679-681), 1569-9293 (November 2010) 


Abstract: Cardiopulmonary bypass during pregnancy is associated with a high fetal and 

maternal mortality. We report a successful pulmonary embolectomy in a woman at the 

27th week of pregnancy; we performed surgical pulmonary embolectomy under 

cardiopulmonary bypass to restore adequate hemodynamic stability and to relieve right 

72

ventricle strain. We discuss the decision made for the preferred anticoagulation drug in 

the setting of heparin-induced thrombocytopenia in the gravida. The pregnancy was 

carried to term and she delivered a healthy boy at 38 weeks of gestation. 2010 Published 

by European Association for Cardio-Thoracic Surgery. 


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32. Treatment of idiopathic thrombocytopenic purpura in pregnancy with pulsed dose 

of dexamethasone 

Author(s): Grgic O., Ivanisevic M., Delmis J. 

Citation: Journal of Obstetrics and Gynaecology, November 2010, vol./is. 30/8(864), 0144- 

3615;1364-6893 (November 2010) 



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33. Fetal genotyping for platelets antigens: A precise tool for alloimmune 

thrombocytopenia: Case report and literature review 

Author(s): Nomura M.L., Couto E., Martinelli B.M., Barjas-Castro M.L., Barini R., Passini 

Junior R., Castro V. 

Citation: Archives of Gynecology and Obstetrics, November 2010, vol./is. 282/5(573-575), 

0932-0067 (November 2010) 


Abstract: Maternal-fetal alloimmune thrombocytopenia complicates about 0.1% of all 

pregnancies and is associated with major fetal and neonatal morbidity and mortality, 

especially spontaneous central nervous system bleeding leading to death and neurological 

handicaps. Successful prevention and treatment depend on the identification of at-risk 

possible carriers of anti-platelet antibodies. Case report: We report a case of a mother 

with a previous child that developed neonatal hemorrhage; HPA-5b anti-platelet 

antibodies were detected post-natally. During the next pregnancy, fetal genotyping 

confirmed the presence of HPA-5b antigen; she was treated with weekly intravenous 

human immunoglobulin and oral prednisone. Pregnancy evolved without remarkable 

features and a full-term baby was delivered, with normal platelet counts. Conclusion: 

Fetal alloimmune thrombocytopenia is a potentially lethal condition, but early detection 

and prevention lead to successful outcome in most cases. 2010 Springer-Verlag. 


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34. A retrospective analysis of obstetric patients with idiopathic thrombocytopenic 

purpura: A single center study 

Author(s): Fujita A., Sakai R., Matsuura S., Yamamoto W., Ohshima R., Kuwabara H., Okuda 

M., Takahashi T., Ishigatsubo Y., Fujisawa S. 

Citation: International Journal of Hematology, October 2010, vol./is. 92/3(463-467), 0925- 

73

5710 (October 2010) 


Abstract: Idiopathic thrombocytopenic purpura (ITP) commonly affects women of 

childbearing age. We studied the clinical characteristics of pregnant women with ITP to 

estimate their risks of bleeding. A retrospective chart review was performed for all 

obstetric patients with ITP who had delivery at our hospital, from 1 March 2000 to 31 

March 2008. Twenty women with ITP delivered 24 children in 23 pregnancies. In all, eight 

women were treated with corticosteroid during their pregnancy period, and there was 

only one non-responder. There was no correlation between the maternal platelet count 

and the amount of blood loss at delivery. Two infants were revealed to have had platelet 

counts lower than 30 x 10 9 /L, and were treated with high-dose IV IgG. One of them also 

received corticosteroid therapy. There was no relationship between maternal platelet 

count at delivery and infant platelet count at birth. Overall, no serious bleeding event was 

seen in either of the mothers or infants. For most women with ITP, pregnancy is 

uncomplicated, and even those with severe thrombocytopenia during pregnancy have 

good outcomes when under the strict care of a hematologist and gynecologist. 2010 The 

Japanese Society of Hematology. 


35. A case of multiple thrombotic thrombocytopenic purpura relapses in pregnancy 

Author(s): Rommens K., Puhl A., Schinzel H., Klbl H. 

Citation: Archives of Gynecology and Obstetrics, October 2010, vol./is. 282/(S77), 0932- 

0067 (October 2010) 


Abstract: Objective: Thrombotic thrombocytopenic purpura (TTP) is a rare but severe 

multisystem disorder. It has for a long time been a pathology that was difficult and 

frustrating to treat with a infaust prognosis. Since the introduction of plasma 

manipulation techniques, particularly plasmaexchange (PE), these patients have benefited 

greatly. Materials and methods: In our case report we introduce a 24 year old pregnant 

woman whose life probably depended on plasma-exchange techniques several times 

during her pregnancy and after the birth of her son. The followup of this woman was 

possible by regularly blood counts because she was a clinically stable patient, known with 

a history of TTPrelapses. But there is still discussion about the most adequate tests of 

diagnosing TTP in pregnant women to differ from hemolysis, elevated liver enzymes and 

low platelets syndrome (HELLP). Conclusions: Both pathologies have parallels in clinical 

signs and laboratory testings but need a different therapy. The deficiency of ADAMTS-13 

activity is suggested to possibly be a prognostic factor of TTP-relapses in pregnancies and 

could be the best indicator to start therapy. On the other hand, the costs make it not 

attractive as a prognostic test. A literature study shows that, because of the rarity of the 

disease there is a need of international cooperative trials to give us more information on 

still unanswered questions. 


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36. Reconsidering fetal and neonatal alloimmune thrombocytopenia with a focus on 

screening and prevention 

Author(s): Skogen B., Killie M.K., Kjeldsen-Kragh J., Ahlen M.T., Tiller H., Stuge T.B., 

Husebekk A. 

74

Citation: Expert Review of Hematology, October 2010, vol./is. 3/5(559-566), 1747-4086 

(October 2010) 


Abstract: Uncertainty regarding the pathophysiology of fetal and neonatal alloimmune 

thrombocytopenia (FNAIT) has hampered the decision regarding how to identify, followup 

and treat the women and children with this potentially serious condition. Since 

knowledge of the condition is derived mainly from retrospective studies, understanding of 

the natural history of this condition remains incomplete. General screening programs for 

FNAIT have still not been introduced, mainly because of a lack of reliable risk factors and 

effective treatment. Now, several prospective screening studies involving up to 100,000 

pregnant women have been published and the results have changed the understanding of 

the pathophysiology of FNAIT and, thereby, the approach toward diagnostics, prevention 

and treatment in a more appropriate way. 2010 Expert Reviews Ltd. 



Systematic review 

Author(s): Kamphuis M.M., Paridaans N., Porcelijn L., De Haas M., Van Der Schoot C.E., 

Brand A., Bonsel G.J., Oepkes D. 

Citation: BJOG: An International Journal of Obstetrics and Gynaecology, October 2010, 

vol./is. 117/11(1335-1343), 1470-0328;1471-0528 (October 2010) 


Abstract: Please cite this paper as: Kamphuis M, Paridaans N, Porcelijn L, De Haas M, van 

der Schoot C, Brand A, Bonsel G, Oepkes D. Screening in pregnancy for fetal or neonatal 

alloimmune thrombocytopenia: systematic review. BJOG 2010;117:1335-1343. 

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially 

devastating disease, which may lead to intracranial haemorrhage (ICH), with neurological 

damage as a consequence. In the absence of screening, FNAIT is only diagnosed after 

bleeding symptoms, with preventive options limited to a next pregnancy. Objectives: To 

estimate the population incidence of FNAIT and its consequences to prepare for study 

design of a screening programme. Search strategy: An electronic literature search using 

MEDLINE, EMBASE and Cochrane database, and references of retrieved articles. No 

language restrictions were applied. Selection criteria: Prospective studies on screening for 

human platelet antigen 1a (HPA-1a) alloimmunisation in low-risk pregnant women. Data 

collection and analysis: Two reviewers independently assessed studies for inclusion and 

extracted data. Main outcome data were prevalence of HPA-1a negativity, HPA-1a 

immunisation, platelet count at birth and perinatal ICH. We aimed to compare outcome 

with and without intervention. Main results: HPA-1a alloimmunisation occurred in 

294/3028 (9.7%) pregnancies at risk. Severe FNAIT occurred in 71/227 (31%) immunised 

pregnancies, with perinatal ICH in 7/71 (10%). True natural history data were not found 

because interventions were performed in most screen-positive women. Authors' 

conclusions Screening for HPA-1a alloimmunisation detects about two cases in 1000 

pregnancies. The calculated risk for perinatal ICH of 10% in pregnancies with severe FNAIT 

is an underestimation because studies without interventions were lacking. Screening of all 

pregnancies together with effective antenatal treatment such as intravenous 

immunoglobulin may reduce the mortality and morbidity associated with FNAIT. RCOG 

2010 BJOG An International Journal of Obstetrics and Gynaecology. 


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75




if required 

38. Fetal/neonatal alloimmune thrombocytopenia (FNAIT): The importance of an 

accurate diagnosis for future pregnancies 

Author(s): Canals C., Ibanez M., Gracia M., Farssac E., Vinyets I., Tarrago M., Nogues N., 

Muniz-Diaz E. 

Citation: Vox Sanguinis, October 2010, vol./is. 99/(22), 0042-9007 (October 2010) 


Abstract: Background: We present the first FNAIT case reported in Spain due to an anti- 

HPA-2b allo-immunization. Case Report: A 35-year old healthy woman gave birth to her 

first child in the 40th week by caesarean section, for obstetric indication. No diathesis was 

observed in the newborn. The platelet count was: 38 x 109/L. No infections or other 

causes of early- onset thrombocytopenia were present. Methods: Platelet auto-antibodies 

in the mother's serum were excluded by immunofluorescent tests (IF). No HLA antibodies 

were detectable (ELISA Quick Screening). The solid phase assay (PAK12) test did not reveal 

alloantibodies against IIb-IIIa glycoprotein (GP), Ib-IX GP or Ia-IIa GP. The MAIPA assay 

allowed us to identify an anti-HPA-2b alloantibody. This finding was consistent with the 

platelet genotype (PCR-SSP). Results: Anti-HPA-3b or HPA-15b antibodies were excluded 

by IF and MAIPA assays. The mother was initially typed as HPA 1b1b by PCR-SSP. Further 

studies showed that she was a carrier of the polymorphism 262T>C, which may lead to 

false HPA-1a negative results by PCR-SSP, and she was actually 1a1b. Conclusion: 

Antibodies were only detectable by MAIPA using a GPIb/IX monoclonal antibody. This fact, 

together with the polymorphism found in the mother, stresses the need to perform the 

appropriate laboratory investigations to identify the antibodies implicated in FNAIT cases. 

An accurate diagnosis is needed in order to ensure a good clinical management in 

subsequent pregnancies. 


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39. Clinical outcomes of intrauterine platelet transfusions in fetomaternal 

alloimmune thrombocytopenia (FMAIT) in England 

Author(s): Lucas G., Calvert A., Green F., Ranasinghe E., Roberts D., Sadani D., Green A. 



Abstract: Background: Management of pregnancies at risk of FMAIT varies according to 

the previous history and between centres. There is a trend away from intrauterine platelet 

transfusions (IUT) because of the associated risks and towards maternal IVIg therapy but 

fetal blood sampling (FBS) continues to be used to monitor responses to IVIg with IUTs 

being given to thrombocytopenic fetuses. Methods: Platelets for IUT were from 

accredited HPA-1a(-)5b(-) donors, lacking red cell, HLA and HPA antibodies. Treatment 

outcomes were followed by contacting the respective centres. Results: FBS was 

performed for 42 pregnancies at risk of severe FMAIT due to HPA-1a (36), 5b (3), 1a+5b 

(2), or 3a (1) antibodies over a 2 year period. Weekly IVIg and IUTs were used to treat 23 

pregnancies and in a further three pregnancies steroids were also used. Five pregnancies 

did not receive IUTs because the fetal platelet counts were satisfactory and 11 

76

pregnancies were treated with IUTs but other treatments were incompletely documented. 

A total of 137 IUTs were given (Range: 0-14 per pregnancy; Mean: 3.7). The mean platelet 

increment was 429 (range 71-881) for 100 evaluable IUTs. Seven neonates required 

further platelet transfusions after birth. There were three deaths following IUT, two 

emergency deliveries for bradycardia after IUT and one intracardiac transfusion following 

a hepatic vein bleed. Intracranial haemorrhages were not detected in the neonates. 

Conclusion: IUTs continue to be used in cases of FMAIT refractory to IVIg therapy. The 

procedure had a combined morbidity/ mortality of 14.3% in this study. 


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40. The usefulness of reticulated platelet count for determining the type of 

thrombocytopenia in pregnant women 

Author(s): Uhrynowska M., Maslanka K., Kopec I., Sakiewicz J., Lopacz P., Orzinska A., 

Brojer E. 



Abstract: Background: Reticulated platelets (RP) are the youngest platelets (PLT) released 

from megacaryocytes. Investigation of RP percentage is useful in patients with plateletconsumptive 

disorders, such as idiopathic thrombocytopenic purpura (ITP). Thrombocytopenia 

(Tcp) in pregnancy affects 6-24% of all pregnancies; ~75% of these cases are 

diagnosed as gestational thromocytopenia (GT). During pregnancy it is difficult to 

distinguish GT from ITP and sometimes from congenital thrombocytopenia (CT). The aim 

of our study was to assess the usefulness of RP count in determining the type of Tcp in 

pregnant women. Methods: Pregnant women: 22 healthy (Control); 49 with Tcp - platelet 

count

haematoma following normal vaginal delivery. She was put on mechanical ventilation and 

managed conservatively with platelet transfusion, Mannitol 1g/kg, Dexamethasone 

1mg/kg and Glycerol 10ml TDS. She regained consciousness and was extubated after 48 

hrs. Repeat CT after 10 days showed no mass effect with resolving haematoma which 

resolved completely after 15 days. Trial of conservative management is safe in pregnant 

patient with ITP who develops subdural haematoma. 


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42. Automated plateletpheresis is safe in second and third trimester pregnant women 

for the treatment of Fetal Alloimmune Thrombocytopenia (FAIT) 

Author(s): Walsh R.P., Arinsburg S.A., Pham H.P., Grima K.M. 

Citation: Transfusion, September 2010, vol./is. 50/(87A-88A), 0041-1132 (September 

2010) 


Abstract: Background: FAIT results from the destruction of fetal platelets (PLTs) by 

transplacental maternal antibodies (Abs) reactive against fetal antigens (Ags) inherited 

from the father. Approximately 50% of cases occur during the first pregnancy and disease 

severity increases in 80-90% of subsequent pregnancies. Most cases are asymptomatic but 

intracranial hemorrhage has been reported in 7-26% of cases with up to a 30% mortality 

rate. Incompatibility in the human PLT Ag system (HPA) is the most common cause, 

usually the result of maternal anti-HPA-1a Abs against HPA-1a Ags on fetal PLTs, but Abs 

against other PLT or human leukocyte Ags can lead to FAIT. Using washed maternal PLTs 

for intrauterine PLT transfusion (IUPT) ensures compatibility as the specific causative 

antibody is not always known. We sought to determine the safety of automated PLT 

apheresis for women during the second or third trimester of pregnancy. Methods: A 

retrospective review of all PLT apheresis procedures on pregnant women at our institution 

from 2/2003 to 11/2008 was performed. An order for PLT apheresis and medical approval 

was obtained from the donors obstetrician 1 week prior to collection. Donors were reevaluated 

one day prior to collection. A nonstress test was performed after the procedure 

to ensure fetal health. All available data including predonation PLT count and hemoglobin 

(Hb), age, gestational age, PLT yield, RBC and plasma loss, length of collection, and 

adverse reactions were recorded. Donors were required to meet all donor criteria 

excluding deferral for pregnancy and Hb

seen in pregnancy. 


Full Text: 




if required. 

43. Animal model of fetal and neonatal immune thrombocytopenia: Role of neonatal 

Fc receptor in the pathogenesis and therapy 

Author(s): Chen P., Li C., Lang S., Zhu G., Spring C., Freedman J., Ni H. 

Citation: Transfusion, September 2010, vol./is. 50/(6A-7A), 0041-1132 (September 2010) 


Abstract: Background: Fetal and neonatal alloimmune thrombocytopenia (FNIT) is a lifethreatening 

bleeding disorder in which maternal antibodies cross the placenta and 

destroy fetal platelets, targeting the platelet glycoprotein GPIIIa (3 integrin). The neonatal 

Fc receptor (FcRn) regulates IgG homeostasis and plays an important role in maternal IgG 

placental transportation. However, the role of FcRn in FNIT has not been adequately 

studied. Methods: Here, we generated a new strain of mice with combined deficiencies of 

3 integrin (3) and FcRn (FcRn). Results: 3FcRnmice mount an immune response and 

generate anti-3 integrin antibodies following immunization with 3/FcRnplatelets. Different 

isotypes of IgGs (both Th1- and Th2-like immune responses) were generated, which 

induced thrombocytopenia. To establish a mouse model of FNIT, we bred 3/FcRnmales 

with immunized 3FcRnfemale mice (immunized twice with 3/FcRnplatelets), and nave 

3/FcRnfemale mice bred with 3/FcRnmales as controls. Anti-mouse 3 integrin IgG was 

detected in these FcRn-negative females (3FcRn-) both during pregnancy and after 

delivery. However, postpartum platelet counts in 3pups (3FcRn-) were not decreased 

compared to controls. FNIT and anti-3 integrin IgG were not observed in these pups. 

Nevertheless, platelet counts were dramatically decreased in pups (3FcRn-/-) delivered 

from immunized, FcRn-positive mice (3FcRn/mothers bred with 3FcRn/males; both 

circulating and platelet-associated anti-3 integrin IgG were detected in pups. To 

distinguish whether maternal or fetal FcRn contributes to FNIT, we bred immunized 

female (3FcRnand 3FcRn) mice with male (3/FcRnand 3/FcRn) mice to generate 3FcRnand 

3FcRnpups. FNIT was only detected in the 3FcRnpups but not in 3FcRnpups, yet they came 

from the same mother. Thus, fetal (not maternal) FcRn was required for transplacental 

IgG transportation and FNIT pathology. To test the therapeutic efficacy of anti-FcRn 

monoclonal antibody in FNIT, anti-FcRn (5 mg/kg) was injected into the immunized 

pregnant 3FcRn/mice. Anti-FcRn downregulated anti-platelet IgG in both the maternal and 

fetal circulations, and ameliorated FNIT. We also found IVIG (1g/kg/week) administration 

decreased the anti-3 integrin IgG in pregnant 3FcRn/and 3FcRnmice, suggesting that IVIG 

downregulates pathogenic IgG via both FcRn-dependent and independent pathways. 

Conclusion: FcRn is required for placental transportation of all isotypes of IgGs and is 

essential for pathogenesis of FNIT. Fetal, but not maternal, FcRn is required for these 

processes and anti-FcRn may be an efficient therapy for FNIT. Our data also demonstrate 

that IVIG downregulated maternal pathogenic antibody via both FcRn-dependent and 

independent pathways. 


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79



if required. 

44. Labor analgesia in patient with immune thrombocytopenic purpura 

Author(s): Schuitemaker Requena J.B., Pantaleon L.L.A., Rodriguez Perez C.L., Tejada Perez 

P., De Armas Marrn N., Emperador F. 

Citation: Regional Anesthesia and Pain Medicine, September 2010, vol./is. 35/5(E171), 

1098-7339 (September-October 2010) 


Abstract: Introduction: Thrombocytopenia occurs in approximately 10% of all 

pregnancies 1 . ITP is responsible of 5%, with an incidence of 1:1000 gestations 2 We present 

a case of a patient with Immune thrombocytopenic purpura (ITP) during pregnancy. Case 

Report: A 34 years old, second gestation, who debuted for ITP in her first pregnancy, she 

was complicated with postpartum hemorrhage due to genital laceration by instrumental 

delivery. She merited the transfusion of 2 red blood cells packages. The newborn 

developed transitory thrombocy-topenia and the thrombocytopenia reverted during the 

puerperium. The laboratory findings at day of admission were: Hb 13 g/dL, Hto 38.5%, 

platelets 81.000/|xl, PT 13.3 seg, PTT 27.9 seg, INR 1.0, Quick index 107%. She was in good 

general conditions. She requested analgesia at 8 cm of cervical dilation and we proposed 

epidural analgesia. With the patient in sit position we perfom an epidural analgesia 

without complications, trougth epidural catheter was administered 10 mL of 0.125% 

bupivacaine plus 100 micrograms of fentanyl. Twenty five min after the first dose and with 

complete cervical dilation, a new dose of 5 mL of 0.2% plain bupivacaine was collocated. A 

newborn was obtained with weight of 3150 g and height 52 cm, Apgar: 9, 10 y 10 points at 

10,50 and 100 minute respectively. The fetal arterial blood gasses were pH 7.176, EB:-4.4. 

During her stay at post anesthetic room, she did not present any eventuality. Platelets 

counts were 87000/mm 3 and the epidural catheter was removed. In conclusion, seems 

safe the realization of neuroaxial blocks with platelets values highest of 50000/mm 3 , and 

we considered a must done request platelets count before the epidural catheter removal. 


Full Text: 

Available in fulltext at the ULHT Library and Knowledge Services' eJournal collection 

45. Successful prevention of thrombotic thrombocytopenic purpura (TTP) relapse 

using monthly prophylactic plasma exchanges throughout pregnancy in a patient with 

systemic lupus erythematosus and a prior history of refractory TTP and recurrent fetal loss 

Author(s): Abou-Nassar K., Karsh J., Giulivi A., Allan D. 

Citation: Transfusion and Apheresis Science, August 2010, vol./is. 43/1(29-31), 1473-0502 

(August 2010) 


Abstract: Background: The occurrence of thrombotic thrombocytopenic purpura (TTP) in 

the setting systemic lupus erythematosus (SLE) is rare. In women of childbearing age, TTP 

is associated with high rates of recurrence in pregnancy. Furthermore, both TTP and SLE 

are associated with a significant risk of adverse pregnancy outcomes. Case presentation: 

We describe the case of a 36. year old female in her first trimester of pregnancy with a 

prior history of SLE-associated severe refractory TTP who was treated with a combination 

of corticosteroids and prophylactic plasma exchanges (PLEX) throughout pregnancy to 

prevent TTP recurrence. She delivered a healthy infant at 33. weeks of gestation after the 

80

onset of preterm labor. There was no evidence of TTP recurrence in the antepartum or 

postpartum period in this high risk patient. Conclusion: Prophylactic PLEX should be 

considered as a therapeutic option to prevent recurrent TTP during pregnancy in high risk 

patients, including patients with previous SLE-associated TTP. 2010 Elsevier Ltd. 


46. Successful pregnancy in a case of congenital thrombotic thrombocytopenic 

purpura 

Author(s): Meti S., Paneesha S., Patni S. 

Citation: Journal of Obstetrics and Gynaecology, July 2010, vol./is. 30/5(519-521), 0144- 

3615;1364-6893 (July 2010) 



Full Text: 


47. A case of pregnancy-induced thrombotic thrombocytopenic purpura with a kidney 

allograft recipient 

Author(s): Iwami D., Harada H., Hotta K., Miura M., Seki T., Togashi M., Hirano T. 

Citation: Clinical Transplantation, July 2010, vol./is. 24/SUPPL. 22(66-69), 0902-0063;1399- 

0012 (July 2010) 


Abstract: A 32-yr-old female patient, who had been suffering from diffuse crescentic 

glomerulonephritis and a consequent end-stage renal disease, successfully underwent 

living-related ABO-incompatible kidney transplantation after a desensitization therapy 

including anti-CD20 monoclonal antibody. Forty-six months after the transplantation, the 

recipient became pregnant. At the 17th gestational week, the patient was admitted for 

the management of pregnancy-induced hypertension and aggressive deterioration of 

kidney graft function. At the 21st gestational week, the patient lost her kidney graft and 

was re-induced into regular hemodialysis. The patient was also suffering from progressive 

hemolytic anemia, thrombocytopenia, and neurologic symptoms with decreased activity 

of von Willebrand factor-cleaving protease, a disintegrin-like and metalloprotease with 

thrombospondin type 1 motifs 13 (ADAMTS13). From these findings and a kidney allograft 

biopsy, the patient was diagnosed as thrombotic thrombocytopenic purpura concurrent 

with acute T-cell-mediated rejection. The patient immediately underwent plasma 

exchange as well as steroid pulse therapy. Despite these treatments, thrombocytopenia 

and intrauterine growth retardation progressed. The patient underwent a caesarian 

section at the 24th gestational week. Consequently, her platelet count recovered 

drastically. However, the patient lost her neonate five d after giving a birth, and the 

patient's graft function had never recovered. 2010 John Wiley & Sons A/S. 


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48. Postpartum plasma exchange in a woman with suspected thrombotic 

thrombocytopenic purpura (TTP) vs. hemolysis, elevated liver enzymes, and low platelet 

syndrome (HELLP): a case study 

81

Author(s): Myers L. 

Citation: Nephrology nursing journal : journal of the American Nephrology Nurses' 

Association, July 2010, vol./is. 37/4(399-402), 1526-744X (2010 Jul-Aug) 


Abstract: The occurrence of a hypercoagulable state and decreasing concentration of 

ADAMTS 13 in late pregnancy and during the postpartum period increases the risk for a 

woman to develop life-threatening thrombotic thrombocytopenic purpura (TTP). This is 

also the time of great risk for the more common obstetric complications of preeclampsia; 

eclampsia; and hemolysis, elevated liver functions tests, low platelets (HELLP) syndrome. 

These conditions are associated with high maternal and perinatal mortality. Differential 

diagnosis may be difficult due to the overlapping of clinical and laboratory findings, 

including thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, 

and renal insufficiency, making it difficult or impossible to distinguish them from TTP. 

Management of microangiopathic disorders encountered during pregnancy differ; 

therefore, an accurate diagnosis is required. Outcomes of TTP without plasma exchange 

therapy (TPE) are almost uniformly fatal. Early recognition and management of symptoms 

with prompt and aggressive TPE is essential when TTP is suspected. 


Full Text: 


49. Fetal and neonatal alloimmune thrombocytopenia 

Author(s): Kaplan-Gouet C. 



Abstract: The fetal and neonatal alloimmune thrombocytopenia results from maternal 

immunization against a specific platelet alloantigen paternally inherited by the foetus. This 

syndrome is the platelet counterpart of haemolytic disease of the neonate, although it 

frequently affects the first infant. The incidence of NAIT has been estimated in unselected 

Caucasian population to be 1/800-1/1000 live births by prospective studies. The most 

feared complication is intracranial hemorrhage (ICH) in the setting of severe 

thrombocytopenia. The morbidity has been estimated to be 20% of the reported cases 

and mortality up to 15%. Since the first description of these conditions in the 1950's by 

Harrington, significant progress has been made in the laboratory diagnosis and 

management of this condition. During pregnancy, fetal thrombocytopenia should be 

suspected in a variety of circumstances: recurrent miscarriages, or ICH which may be 

diagnosed by sonography. In the neonate, alloimmune thrombocytopenia (NAIT) is the 

commonest cause of early onset isolated thrombocytopenia in an otherwise healthy 

newborn. NAIT is usually discovered incidentally when a full-term neonate born to a first 

time pregnant healthy mother has petechiae, purpura or, less frequently, overt visceral 

bleeding at birth or a few hours afterwards. ICH may be present at birth or can occur as 

long as the newborn is severely thrombocytopenic. The diagnosis of NAIT is suspected 

when other causes of thrombocytopenia are excluded. However, the infant may be 

asymptomatic, with thrombocytopenia discovered incidentally. Therefore, unexpected or 

unexplained neonatal thrombocytopenia or early onset of severe thrombocytopenia in 

both pre-term and term babies should raise the possibility of NAIT and guide 

investigations accordingly. The risk of life-threatening hemorrhage necessitates prompt 

diagnosis and effective therapy. The laboratory diagnosis is of utmost importance for the 

management of the affected infant and the subsequent pregnancies. The diagnosis is 

straightforward when a maternal alloantibody is detected directed against the offending 

82

antigen present in the infant. The molecular basis of the platelet alloantigens has been 

elucidated and a number of genotyping methods have been developed: PCR-RFLP, PCR- 

SSP, real time PCR and more recently microarrays. Although genotyping is widely used, 

unknown genetic variants may alter the results, and ethnic diversity is of importance. The 

detection of the alloantibodies could be challenging. Currently the most widely techniques 

used are the antigen-capture assays with mouse monoclonal antibodies (MAIPA 

technique). Alloantibody heterogeneity should be taken into consideration. Detection of 

alloantibodies directed against low frequency antigens is somehow more complicated. 

New techniques are developed to overcome these problems. When the diagnosis is 

equivocal, retesting is recommended with new samples. Difficulties in laboratory 

diagnosis should not delay therapy when there is bleeding tendency or severe 

thrombocytopenia. Severe neonatal thrombocytopenia necessitates platelet transfusions. 

Antenatal management has been developed due to the high rate of recurrence for 

subsequent incompatible fetuses, with usually a more severe condition. Maternal therapy 

with weekly IVIG with or without corticosteroids and reduction of invasive procedures are 

considered as first line approach. 


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50. Evaluation of antenatal thrombocytopenia in 115 women attending a tertiary 

centre, together with neonatal platelet counts: Can this information help in antenatal 

counselling 

Author(s): Rajeswary J., Myers B. 

Citation: Archives of Disease in Childhood: Fetal and Neonatal Edition, June 2010, vol./is. 

95/(Fa57), 1359-2998 (June 2010) 


Abstract: The aim of this study was to evaluate the maternal platelet count in women 

diagnosed antenatally with thrombocytopenia (platelet count < 100) from any cause, 

neonatal outcome, and, where available, the corresponding neonatal platelet count. The 

authors wanted the information in our population to guide us in the following: (1) for 

antenatal counselling, as most women diagnosed with thrombocytopenia are anxious 

regarding foetal and neonatal outcomes, (2) Guidance in managing those babies who did 

not have a cord blood count done at birth. 115 women with thrombocytopenia were 

identified from laboratory records over a 3-year period from a tertiary care unit in a 

combined Obstetric haematology clinic. Of the 115 maternities, neonatal platelet counts 

were available only on 44 babies (38.2%), of which there were only 2 babies with a count 

of less than 100 (4 %) was noted Of the 71 babies who did not have a count one was 

stillbirth, due to severe preeclampsia, IUGR and prematurity, none had any notable 

neonatal problems. This information is helpful in antenatal counselling of women who are 

found to have thrombocytopenia in pregnancy. It will help reduce maternal anxiety 

regarding neonatal outcomes. Also these data encourage us to look at larger numbers and 

decide if the authors need to do neonatal counts as a routine if a cord blood sample has 

been missed. 


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51. [Clinical analysis of pregnancy complicated with severe thrombocytopenia] 

83

Author(s): Wang D.P., Liang M.Y., Wang S.M. 

Citation: Zhonghua fu chan ke za zhi, June 2010, vol./is. 45/6(401-405), 0529-567X (Jun 

2010) 


Abstract: To investigate the etiology and perinatal outcome of pregnancies complicated 

with extremely severe thrombocytopenia [at least two times of platelets count (PLT) < 10 

x 10(9)/L during pregnancy]. Clinical data, including basic information, etiology, 

management and outcomes of pregnant women with extremely severe 

thrombocytopenia, admitted to Peking University People's Hospital from January 2004 to 

March 2009, were retrospectively collected. The management of these cases varied 

according to different etiology and the symptoms: (1) PLT were maintained > 20 x 10(9)/L 

and hemoglobulin > 70 g/L in those women without spontaneous bleeding; (2) PLT 

transfusion would be required when PLT < 10 x 10(9)/L or bleeding occur and RBC would 

be supplied when hematocrit < 25% and hemoglobulin < 70 g/L; (3) Hemoglobulin should 

be > 70 g/L and PLT > 30 x 10(9)/L before cesarean section or delivery; (4) Predinisone 

and/or intravenous immunoglobulin G (IVIG) would be given in women complicated with 

idiopathic thrombocytopenic purpura (ITP) when PLT < (20 - 30) x 10(9)/L or bleeding. PLT 

would be given if all the above management were failed, or PLT < 10 x 10(9)/L, or 

bleeding. Women without bleeding would be closely monitored and delivery would be 

planned. (1) Twenty-six cases were identified among 9302 deliveries during the study 

period (0.28%), with an average of maternal age of 29. Seventeen were diagnosed before 

conception and 9 during pregnancy. Among the 26 women, half received regular prenatal 

check in our hospital and the average gestations at diagnosis was 24 weeks and the other 

half without regular prenatal visits and the average gestations at diagnosis was 32 weeks. 

Etiology was identified in 24 out of the 26 women, including 14 (54%) ITP, 5 

myelodysplastic syndrome (MDS), 4 chronic aplastic anaemia (CAA) and 1 systemic lupus 

erythematosus (SLE). (2) Management: All of the 26 women received blood products. 

Among the 14 ITP cases, 6 received predinisone and IVIG and 8 only took predinisone. 

Nine of the 26 patients (35%) had pregnant complications, among which 6 (6/9) were 

preeclampsia. The overall average gestation at delivery was 36 weeks. Only 2 delivered 

vaginally with the average blood loss of 83 ml and 23 cesarean sections were performed 

with the average blood loss of 410 ml. (3) Perinatal outcomes: There were 26 perinatal 

babies, among which 1 died intrauterine and 25 were born alive (12 preterm infants). The 

average birth weight was 2877 g. Neonatal severe thrombocytopenia presented in 2 

newborns whose mother complicated with ITP. The main cause of extremely severe 

thrombocytopenia during pregnancy is ITP, managed mainly by predinisone and IVIG, 

followed by CAA and MDS, which may require supportive treatment. Pregnancy 

complicated with extremely severe thrombocytopenia is not an indication of termination. 

Better maternal and fetal outcomes can be achieved through proper treatment based on 

the etiology, intensive care in prevention and management of complications and cesarean 

section. 


52. Preimplantation genetic diagnosis as a strategy to prevent a fetomaternal 

incompatibility for a highly immunogenic platelet antigen causing severe fetal/neonatal 

alloimmune thrombocytopenia (FNAIT) 

Author(s): Freixa L., Nogues N., Martnez-Pasarell O., Lpez O., Canals C., Bassas L., Muiz- 

Diaz E. 

Citation: Reproductive BioMedicine Online, May 2010, vol./is. 20/(S15-S16), 1472-6483 

(May 2010) 

84


Abstract: FNAIT is an immunological complication of the gestation caused by maternal IgG 

antibodies that recognize fetal platelet antigens inherited from the father. 

Alloimmunization against the HPA-1a antigen is the cause of aprox. 85% of the FNAIT 

cases in caucasians. Women at risk are only identified after a previous child with FNAIT 

and the antenatal treatment of alloimmunized women in subsequent pregnancies is 

controversial and not always effective. Aim: To set up and validate a preimplantation 

genetic diagnosis protocol based on genotyping the HPA-1a/1b polymorphism from single 

blastomeres in order to avoid the fetomaternal HPA-1a incompatibility. Materials and 

Methods: Single blastomeres from previously HPA-1 typed couples were obtained by 

embryo biopsy. The corresponding genomic DNA was amplified by a modified Multiple 

Displacement Amplification procedure using components of the GenomiPhi v.2 kit. 

Subsequent analysis of the blastomere's HPA-1 genotype was carried out by Real-time 

PCR with allele-specific TaqMan MGB probes. In parallel, a set of previously selected 

microsatellite markers were amplified using labeled primers and the allelic profile was 

determined by capillary electrophoresis. A total of 14 couples participated in the 

validation study. After obtaining informed consent of these couples, whole embryos not 

selected for transfer were collected. A total of 70 blastomeres, corresponding to 36 

embryos, were tested during this evaluation. Results: We have selected a set of 

microsatellite markers adjacent to the HPA-1 locus and have assessed their informativity 

in a study including 10 familial FTNAI cases with previously known HPA-1a incompatibility. 

A PGD protocol for the detection of HPA-1a negative embryos has been set up, which 

includes the analysis of 3 extragenic (D17S1183, D17S806, D17S1827) and 1 intragenic STR 

markers. This protocol has been tested in a validation study with single blastomeres (n = 

70). Preliminary data analysis indicates an ADO rate of aprox. 15% but we have been able 

to identify all HPA-1a false negative embryos with the STRs genetic linkage. As an attempt 

to reduce the incidence of ADO, a modification of the current protocol consisting of the 

addition of locus-specific primers to the reaction mix during the MDA step is currently 

evaluated. Conclusions: This PGD approach offers new prospects to HPA-1a alloimmunized 

women with a heterozygous husband and a previous history of an affected NAIT child. The 

protocol here described allows to avoid the HPA-1a incompatibility through the selection 

of the embryo(s) to be transfered. 


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pregnancy 

Author(s): He Y., Chen Y., Zhao Y., Zhang Y., Yang W. 

Citation: International Journal of Laboratory Hematology, May 2010, vol./is. 32/(172-173), 

1751-5521 (May 2010) 


Abstract: Objectives: Thrombotic thrombocytopenic purpura (TTP) is a rare lifethreatening 

disorder characterized by microangiopathic haemolytic anaemic and 

thrombocytopenia. TTP occurs occasionally late in pregnancy or immediately after 

delivery. To investigate the early recognition and management of pregnancy in women 

with thrombotic thrombocytopenic purpura (TTP) using emergency plasma exchange. 

Methods: Five cases of TTP were evaluated retrospectively. Clinical and laboratory 

findings, von Willebrand factor (vWF)- cleaving metalloprotease (ADAMTS13) activity, and 

maternal and neonatal outcome were recorded and analyzed. Results: Five cases were all 

85

nulliparous. ADAMTS13 assay was performed, and the enzyme activity was less than 5% of 

the normal controls in three cases. Gene mutation in the 9th exon causing amino acid 

exchange 349Arg->Cys in ADAMTS13 was identified in one patient. After treatment 

including infusion of fresh-frozen plasma (n=4), packed red blood cells (n=5), platelet 

transfusions (n=2) and /or continued renal replacement therapy (CRRT) (n=1), plasma 

exchange (n=2), three patients were alive, one died on postpartum day 6 in hospital 

without plasma exchange, and one of familial TTP died 3 months after dischange. 

Conclusions: TTP complicating pregnancy is rare and associated with high maternal 

mortality. The sign of thrombocytopenic and microangiopathic hemolytic anemia before 

and after delivery, especially patients with HELLP syndrome highly suggest the diagnosis. 

Improved survival after this disorder has been attributed to aggressive treatment with 

plasma transfusion or plasmapheresis. 


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54. Thrombocytopenia in plasmodium parasitized pregnant women in the niger delta 

of Nigeria 

Author(s): Osaro E., Zachaeus J., Charles A., Miebaka H. 

Citation: International Journal of Laboratory Hematology, May 2010, vol./is. 32/(155-156), 

1751-5521 (May 2010) 


Abstract: Objectives: Malaria infection during pregnancy is a major public health problem 

in tropical and subtropical regions of the world. Haematological changes associated with 

malaria in pregnancy are not well documented, and have focused predominantly on 

anaemia. The aim of this study was to determine the impact of Plasmodium parasitaemia 

on the platelet count of pregnant women in the Niger Delta of Nigeria. Methods: : In this 

observational study we reviewed the platelet counts from routine complete blood count 

(CBC) in a cohort of healthy (pregnant and nonpregnant) and malaria-infected pregnant 

women attending antenatal clinics. A platelet count of 100 x 109/L was the threshold at 

two standard deviations below the mean for healthy Nigerian pregnant women used to 

indicate thrombocytopenia. Differences in platelet counts were compared based on 

malaria species and parasitemia in matched nonpregnant and pregnant women. Blood 

smears from Quantitative Buffy Coat malaria-positive samples stained with Giemsa were 

used for determination of parasite load and specie identification by light microscopy. 

Results: The mean platelet counts (x10 9 /L) were significantly lower in pregnant subjects 

with an episode of Plasmodium falciparum malaria 111.3 +/- 9.3 x 109/L compared to 

nonparasitized and healthy nonpregnant controls (255.09 +/- 24.10 and 270 +/- 51.5 x 

109/L) respectively. Platelet count values were 112.5 +/- 9.68 x 109/L and 126.3 +/- 

16.7x109/L for the primigravidae and multigravidae respectively. (chi2= 10.46; P = 0.05). 

Parasite density was significantly higher among Plasmodium parasitized primigravidae 

compared to multigravidae 2150 (1638-2662) parasites/muL in primigravidae women 

compared to 1826 (1430-2222) parasites/muL in multigravid women. The mean parasite 

count in Plasmodium falciparum parasitized subjects was 2650 +/- 234 parasites/muL, 

95% confidence interval (2092-3118). Malaria parasite was found to exert a significant 

reduction in platelet density in parasitized subjects. This reduction was more pronounced 

in primigravidae and multigravidae. An inverse relationship was established between 

parasite density and platelet count (y = - 0.020 x + 86.2, r = -0.3). Conclusions: There is 

need for a strengthened antenatal care system with increased awareness of the problem 

among communities most affected by malaria .Preventative strategies including regular 

chemoprophylaxis, intermittent preventative treatment with antimalarials and provision 

86

of insecticide-treated bed nets should be implemented as well as integration of malaria 

control tools with other health programmes targeted to pregnant women and newborns. 


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55. Fetomaternal alloimmune thrombocytopenia (FMAIT) in the UK: A prospective 

national study of incidence and outcomes using obstetric, paediatric and laboratory 

reporting systems 

Author(s): Allen D., Knight M., Pierce M., Spark P., Roberts D.J., Murphy M.F. 

Citation: British Journal of Haematology, May 2010, vol./is. 149/(11), 0007-1048 (May 

2010) 


Abstract: FMAIT is the commonest cause of severe neonatal thrombocytopenia in 

otherwise well term infants and can lead to serious bleeding, intracranial haemorrhage 

and death. There is current debate about the efficacy of antenatal screening for the 

condition. The aim of this study was to address the deficiency in basic epidemiological 

data on FMAIT in order to inform this debate. Parallel national descriptive studies were 

conducted using the UK Obstetric Surveillance System (UKOSS) and the British Paediatric 

Surveillance Unit (BPSU) for a two year period from October 2006. Cases were crosschecked 

with the NHS Blood and Transplant laboratories. Data from the three sources 

were matched and the overall incidence was estimated using capture-recapture 

techniques. One year follow-up data was sought through the BPSU. There were 175 cases 

of FMAIT identified through the three sources over a period of two years. After capture 

recapture analysis, 196 cases were estimated to have occurred (95%CI 185-208) in 

1,332,642 total births, giving an estimated incidence of 1.3 cases per 10,000 births (95%CI 

1.1-1.5). There were 9 known pregnancy losses/deaths amongst the 175 cases (one 

miscarriage, 3 terminations, 3 stillbirths and two infant deaths). An additional 20 (14%) 

infants had an intracranial haemorrhage; disability after one year was reported in 11 

infants (9%). Of those cases with an adverse outcome, only 23% had a known family 

history of FMAIT. The incidence of clinically detected FMAIT estimated from this national 

study is less than one sixth of that estimated from prospective screening studies. Almost 

three quarters of cases with serious clinical problems did not have a known family history 

of FMAIT, highlighting the importance of appropriate assessment of the case for antenatal 

screening. This study represents a major contribution to the epidemiology of FMAIT in the 

UK. 


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56. Successful management of term pregnancy complicated with deep vein 

thrombosis and heparin-induced thrombocytopenia 

Author(s): Sioulas V., Mourtzakis S., Salamalekis G., Karanikolopoulos P., Chrelias C., 

Grouzi E., Brountzos E., Kassanos D. 

Citation: Journal of Maternal-Fetal and Neonatal Medicine, May 2010, vol./is. 23/(211), 

1476-7058 (May 2010) 


Abstract: Brief Introduction: The aim of this study is to present a case of deep vein 

87

thrombosis (DVT) and heparin-induced thrombocytopenia type II (HIT II) during term 

pregnancy, treated with inferior vena cava (IVC) filter insertion and fondaparinux 

administration. Clinical Cases or Summary Results: A 31-yearold nulliparous woman at 37 

weeks of gestation was referred to our Department for further management of left 

popliteal vein thrombosis. Her medical history was significant for systemic lupus 

erythematosus and a prior episode of DVT. During the course of pregnancy, she was 

treated with azathioprine, dexamethasone and tinzaparin (4500 U/24 h). On admission, 

the woman was switched to IV infusion of unfractionated heparin, but, 24 h later, a 

marked decrease in platelet count was recorded. Functional and ELISA assays confirmed 

the diagnosis of HIT. An IVC filter was inserted and the patient underwent cesarean 

section. A baby boy weighing 2510 gr, with umbilical artery pH of 7.32 and Apgar score of 

7/1'9/5', was delivered. Postpartum anticoagulation consisted of fondaparinux (7.5 mg/24 

h), gradually replaced by oral anticoagulants, for a period of 6 months. IVC filter was 

removed 5 weeks after deployment. Conclusions: Fondaparinux, an alternative option for 

the treatment of HIT, may be safely used in pregnant or lactating women. However, when 

therapeutic anticoagulation is contraindicated or fails, the placement of IVC filter during 

pregnancy complicated with DVT is not, probably, associated with adverse maternal or 

fetal outcomes. 


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57. Thrombocytopenia during pregnancy - More than one disease 

Author(s): Vladareanu R., Nicolescu A., Vladareanu A.M. 

Citation: Journal of Maternal-Fetal and Neonatal Medicine, May 2010, vol./is. 23/(76), 

1476-7058 (May 2010) 


Abstract: Thrombocytopenia, complicating up to 10% of all pregnancies may result from 

very many causes. The presence of thrombocytopenia in pregnant women demandes to 

exclude false thrombocytopenia and imposes the need for a correct clinical, etiological 

and serological diagnosis in order to apply a better treatment and also provide a better 

monitoring of the pregnancy. Distinction between ITP and gestational thrombocytopenia 

may be difficult when thrombocytopenia is first discovered during pregnancy. Autoantibodies 

are the hallmark of autoimmunity, and they are not found in gestational 

thrombocytopenia. In case of ITP, the detection of the antiplatelet antibodies may be 

useful in monitoring the evolution of the disease and treatment efficiency. Serious 

maternal risks are uncommon, therefore more conservative management should be 

applied. However, the therapy is required if thrombocytopenia is below 50x109/L or 

hemorrhagic syndromes occurs. Maternal therapy implies: Corticosteroids (later response; 

safe for the fetus and adverse events for the mother); Intravenous immunoglobulins 

(rapid response, indicated in the predelivery period or in case of failure to corticosteroids), 

splenectomy (rarely done in 2nd trimester) and new therapies (Romiplostim, Rituximab). 

Short-term administration of the thrombopoesis-stimulating protein, Romiplostim, has 

been shown to increase platelet counts in most patients with ITP. Transplacental passage 

of maternal autoantibodies could lead to fetal/ neonatal thrombocytopenia. The 

characteristics of the biological maternal parameters may be predictive for the 

assessment of possible fetal or neonatal complications (intracerebral haemorrhage appear 

only in 0-3% of cases). Close monitoring is necessary. 


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88


58. Prenatal diagnosis of fetal intracranial hemorrhage in pregnancy complicated by 

idiopathic thrombocytopenic purpura 

Author(s): Koyama S., Tomimatsu T., Sawada K., Kanagawa T., Isobe A., Taniguchi Y., Wada 

T., Kimura T., Arahori H., Kitabatake Y., Wada K. 

Citation: Prenatal Diagnosis, May 2010, vol./is. 30/5(489-491), 0197-3851;1097-0223 (May 

2010) 



59. Retrospective comparison of maternal vs. HPA-matched donor platelets for 

treatment of fetal alloimmune thrombocytopenia 

Author(s): Giers G., Wenzel F., Fischer J., Stockschlader M., Riethmacher R., Lorenz H., 

Tutschek B. 

Citation: Vox Sanguinis, February 2010, vol./is. 98/3 PART. 2(423-430), 0042-9007;1423- 

0410 (February 2010) 


Abstract: Background and Objectives: In fetal alloimmune thrombocytopenia (FAIT), 

transplacental maternal antibodies cause destruction of fetal platelets. FAIT is similar to 

fetal Rhesus haemolytic disease, but half of the affected fetuses are born to primiparous 

women. In 10-20% of cases, prenatal and perinatal intracranial haemorrhages are 

reported. Different therapeutic approaches have been described, including maternally 

administered high-dose intravenous immunoglobulin (high dose IVIG) without or with 

steroids or intrauterine transfusion (IUT) of compatible platelets. For the latter, the use of 

plasma-free maternal and donor platelets has been described, but a comparison of these 

two sources of platelets has not been reported. Materials and Methods: We 

retrospectively analyzed the clinical courses of cases with FAIT treated with IUT of either 

HPA-matched donor platelets or maternal platelets, done by a single team between 1990 

and 1997. In 57 pregnancies, FAIT was treated by repeated IUT with either maternal (15 

fetuses) or donor platelets (42 fetuses). Results: There was no procedure-related fetal or 

neonatal loss. Platelets from both sources reliably raised the fetal platelet counts. Donor 

platelet preparations contained more platelets and yielded higher fetal post-transfusion 

platelet counts, but maternal platelets were clinically equally effective. Conclusions: 

Donor and maternal platelet concentrates are effective sources for the treatment of FAIT. 

2009 The Author(s). 


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60. Antithrombin concentrate as a treatment of preeclampsia induced thrombopenia: 

Thromboelastometric and biological data 

Author(s): Ducloy-Bouthors A.S., Tournoys A., Wibaut B., Deruelle P., Bauters A. 

Citation: Pathophysiology of Haemostasis and Thrombosis, 2010, vol./is. 37/(A82), 1424- 

8832 (2010) 


Abstract: Preeclampsia (PE) is a major cause of maternal death. Thrombopenia is observed 

89

in 15% of the severe PE and may be explained by immunologic or microthrombotic or 

microangiopathic comsumptive mechanisms. Drastic decrease in platelet count is a 

criteria for pregnancy medical termination. In this case report, a severe PE with 

thrombopenia and acquired antithrombin (AT) deficiency was treated with AT concentrate 

(Aclotine LFB France) and monitored by thromboelastometry (ROTEM Pentapharm 

Munich). Case: Mrs V.S . 5pare, 38SG, 28 years old, BMI 39 kg/m 2 , was admitted in a 

tertiary care obstetric unit for severe preeclampsia: moderate hypertension, epigastric 

pain, platelet count: 37,109/mm3, elevated hepatic enzymes >10 N, hemolysis. Induction 

of labor was decided. Laboratory results and ROTEM showed a hypercoagulable state and 

AT deficiency 40%. (CT and CFT were decreased, alpha angle and MCF in normal range and 

FIBTEM amplitude increased). AT concentrate (Aclotine LFB France) [1000 UI/30 minutes 

then 2000 UI/12h] was administered in order to obtain AT activity 72% and platelet count 

99 109/mm3. Haemostasis remained in the normal range for the course of labor and 

caesarean section (Table). No postpartum haemorrhage HPP=950 ml was observed. Postpartum 

treatment was nicardipine and enoxaparine 26000 UI/j. Mother and child 

discharged at Day 5 from from the hospital without complication. Decrease in AT activity 

is known to predict the severity of preeclampsia. Terao and Paternoster have studied the 

benefit of AT administration on the course of maternal and foetal disease (2, 3). However 

AT is used carefully because of a potential increase in hemorrhagic risk. In this case report, 

hypercoagulability, AT efficacy and safety are documented by thromboelastometry. Table 

presented here. 


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61. Thrombotic thrombocytopenic purpura (TTP) and pregnancy: Presentation and 

management in subsequent pregnancies 

Author(s): Thomas M.R., Camilleri R.S., MacHin S.J., Scully M.A. 

Citation: Pathophysiology of Haemostasis and Thrombosis, 2010, vol./is. 37/(A4), 1424- 

8832 (2010) 


Abstract: Background/Aims: Half of all patients with acute TTP are women of child bearing 

age. Increasing use of ADAMTS13 assays and mutational analysis has improved pregnancy 

management. Materials and Methods: All UK cases of TTP referred for ADAMTS13 analysis 

or managed at UCLH were included. Results: 8/16 cases of acute TTP presenting in 

pregnancy had congenital TTP. Diagnosis was confirmed by ADAMTS13 activity

pregnancy. Women with congenital TTP require therapy throughout pregnancy. In women 

with previous acquired TTP, baseline ADAMTS13 activity and antibody status may identify 

likely relapse. Elective PEX should be considered in women with reduced ADAMTS13 (

clinical trials. Agents that target ADAMTS13 autoantibody production by B-cells, such as 

anti-CD20 monoclonal antibodies, have the potential to shorten the duration of plasma 

exchange treatment, reduce relapses, and transform the management of this once 

enigmatic disorder. 2010 The Japanese Society of Hematology. 


64. Pathophysiology of thrombotic thrombocytopenic purpura 

Author(s): Tsai H.-M. 

Citation: International Journal of Hematology, January 2010, vol./is. 91/1(1-19), 0925- 

5710 (January 2010) 


Abstract: Thrombotic thrombocytopenic purpura (TTP) is a disorder with characteristic 

von Willebrand factor (VWF)-rich microthrombi affecting the arterioles and capillaries of 

multiple organs. The disorder frequently leads to early death unless the patients are 

treated with plasma exchange or infusion. Studies in the last decade have provided ample 

evidence to support that TTP is caused by deficiency of a plasma metalloprotease, 

ADAMTS13. When exposed to high shear stress in the microcirculation, VWF and platelets 

are prone to form aggregates. This propensity of VWF and platelet to form microvascular 

thrombosis is mitigated by ADAMTS13, which cleaves VWF before it is activated by shear 

stress to cause platelet aggregation in the circulation. Deficiency of ADAMTS13, due to 

autoimmune inhibitors in patients with acquired TTP and mutations of the ADAMTS13 

gene in hereditary cases, leads to VWF-platelet aggregation and microvascular thrombosis 

of TTP. In this review, we discuss the current knowledge on the pathogenesis, diagnosis 

and management of TTP, address the ongoing controversies, and indicate the directions of 

future investigations. 2010 The Japanese Society of Hematology. 


65. Thrombocytopenia in pregnancy 

Author(s): McCrae K.R. 

Citation: Hematology / the Education Program of the American Society of Hematology. 

American Society of Hematology. Education Program, 2010, vol./is. 2010/(397-402), 1520- 

4383 (2010) 


Abstract: Thrombocytopenia occurs commonly during pregnancy, and may result from 

diverse etiologies. Awareness of these many causes facilitates proper diagnosis and 

management of thrombocytopenia in the pregnant setting. Some causes of 

thrombocytopenia are unique to pregnancy and may not be familiar to hematologists. In 

the review, we will discuss the differential diagnosis of thrombocytopenia in pregnancy, 

and the pathogenesis of selected thrombocytopenic disorders. Considerations for optimal 

management of the pregnant patient with thrombocytopenia will also be described. 


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66. High LDH to AST ratio: Rapidly available aid to support a suspected diagnosis of 

pregnancy-related thrombotic thrombocytopenic purpura 

Author(s): Keiser S., Boyd K., Rehberg J., Elkins S., Owens M., Martin J. 

92

Citation: American Journal of Obstetrics and Gynecology, December 2009, vol./is. 201/6 

SUPPL. 1(S286), 0002-9378 (December 2009) 


Abstract: OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) is rarely encountered 

during pregnancy or the puerperium. Diagnosis is challenging as TTP can mimic severe 

preeclampsia/HELLP syndrome; definitive laboratory testing remains protracted and 

problematic. This study sought to explore the disease course, treatment, maternalperinatal 

outcomes and the LDH-to-AST ratio findings in a single institution series of 

gestational/puerperal patients considered to have TTP. STUDY DESIGN: Retrospective 

review of all pregnant/puerperal patients with TTP from a single tertiary care center 

during 1986-2006. Data were collected and analyzed, and are reported as median (range) 

or percentage. RESULTS: 13 pregnant (N=10) or puerperal (N = 3) patients with TTP were 

identified; 11 cases were primary, 2 were recurrent. Gestational age at diagnosis for 

pregnancy cases was 36 (22-39) weeks. Most TTP patients in this series (53.9%) were 

considered initially to have severe preeclampsia/HELLP. Three (23.1%) were febrile and 

one (7.7%) had seizures. Laboratory findings included an LDH to AST ratio of 61 (22-185), 

indirect bilirubin 1.65 (0.66-4.68) mg/dL, peak serum creatinine 1.60 (0.7-9.6) mg/dL, 

platelet nadir 18 (7-105)K/uL, and schistocytes with hematuria were uniformly present. 

ADAMTS-13 values were not available. No patient improved in response to delivery. Two 

maternal (15.4%) and eight perinatal (61.5%) deaths occurred. Four patients subsequently 

developed chronic renal failure. All TTP patients underwent serial plasma exchanges (PEX), 

92.3% received corticosteroids, 69.2% required antihypertensives and 23.1% received 

sulfinpyrazone. CONCLUSION: Because pregnancy-associated TTP is associated with a 

significant risk of morbidity and mortality for both patient and progeny, emergently 

differentiating between preeclampsia/HELLP syndrome and TTP is critical. Until rapid, 

sensitive and specific testing for TTP is readily available, we recommend considering a 

very high LDH to AST ratio, a very low platelet count and hematuria to be suggestive of 

TTP for emergency PEX management purposes. 


67 Advances in alloimmune thrombocytopenia laboratory investigations 

Author(s): Kaplan C. 

Citation: Vox Sanguinis, November 2009, vol./is. 97/(24), 0042-9007 (November 2009) 


Abstract: Alloimmune thrombocytopenia is mainly encountered during pregnancy when 

the mother becomes immunized against the fetal platelets antigens she lacks. Therefore 

during pregnancy the maternal IgG cross the placenta and recognize their target on the 

fetal platelets. The resulting fetal alloimmune thrombocytopenia, which incidence has 

been evaluated to 1/ 1000 live births in Caucasians, is usually severe and can lead to 

bleeding. Intracranial hemorrhage (20-30% in retrospective studies) is the most severe 

complication leading to death (10-15%) or neurological sequelae (20%). Due to the 

recurrence for incompatible fetuses in the subsequent pregnancies, antenatal 

management has been developed. The diagnosis of fetal or neonatal alloimmune 

thrombocytopenia is of utmost importance for the management of the affected infant and 

the subsequent pregnancies. The diagnosis is straightforward when a maternal 

alloantibody is detected directed against the offending antigen present in the infant. The 

molecular basis of the platelet alloantigens has been elucidated and single nucleotide 

polymorphism (SNP) in the gene encoding the relevant glycoprotein is present in the 

23/24 defined antigens. Antigen determination has evolved during the recent years. A 

number of genotyping methods have been developed: PCR-RFLP, PCR-SSP, real time PCR 

and more recently microarrays. Although genotyping is widely used, unknown genetic 

93

variants may alter the results, and ethnic diversity is of importance. Genotype is not 

always phenotype. However phenotyping is somehow problematic because reference 

human sera have limited availability. The detection of the alloantibodies could be 

challenging. Currently the most widely techniques used are the antigen-capture assays 

with mouse monoclonal antibodies. However false-negative results may occur by steric 

hindrance between the human antibody and the monoclonal antibody. Excessive washing 

procedure may result in the dissociation of low avidity alloantibodies. In addition 

modification of the epitope during storage should be taken into account. Alloantibodies 

are heterogeneous, anti HPA-1a undetectable with the MAIPA technique HPA-1a, >, are detectable with surface plasmon resonance technology. Some anti 

HPA-3a alloantibodies are detectable only using fresh platelets in flow cytometry assays. 

Detection of alloantibodies directed against low frequency antigens is somehow more 

complicated. Cross-match with maternal sera and paternal platelets is to be performed. 

However it depends on paternal platelets availability and ABO mismatch. New techniques 

are developed to overcome these problems such as B-lymphoblastoid cell lines, stably 

transfected CHO cells and recombinant mini-b3 integrin fragments. Due to variation in 

sensitivity of antibody detection among laboratories and the absence of monoclonal 

antibodies against human platelet antigens, only HPA-1a antibodies have been made up to 

now, international standard reagents for detection of human antibody against human 

platelet antigen have also been developed: Anti HPA-1a for quantification, anti HPA-5b, 

anti HPA-3a and minimum sensitivity for anti HPA-1a. Difficulties in laboratory diagnosis 

for fetal and neonatal alloimmune thrombocytopenia should not delay therapy when 

there is bleeding tendency or severe thrombocytopenia. When the diagnosis is equivocal, 

retesting is recommended with new samples. In conclusion, international workshop 

exercises are of importance for further improvement and quality assurance proficiency. 


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68. Therapy for chronic ITP in Germany - A patient survey 

Author(s): Matzdorff A.C., Arnold G., Salama A., Ostermann H., Hummler S. 

Citation: Blood, November 2009, vol./is. 114/22, 0006-4971 (20 Nov 2009) 


Abstract: Background: Guidelines recommend glucocorticoids and splenectomy as 

standard 1st and 2nd line treatments for chronic ITP. We sought to find out how German 

ITP-patients are treated in respect of these guidelines. Methods: Members of a patient 

support association >18 y with self-reported history of chronic ITP (>6 mo) were surveyed. 

A questionnaire was developed from literature review with clinician and patient input, 

and administered on-line. Results: 123 questionnaires were evaluated. Age (median 51 

years) and gender distribution (38% m, 62% f) are comparable to surveys from other 

countries. 70% of patients had chronic ITP for more than 5 years and 50% a usual platelet 

count of < 50.000/6l (20% < 30.000/mul). 69% had hematomas or petechiae within the 

last 12 months, 45% had oropharyngeal bleeds, and 11% had been admitted to a hospital 

within this year. 88% had received or receive glucocorticoids, 28% were splenectomized. 

IVIg was given to 55%, rituximab to 22%, anti-D to 11%, cyclosporine to 7%. 

Complementary and alternative medical treatments had been used by 36%. 38 women 

were under the age of 50 and 14 (36%) reported that they had been advised not to 

become pregnant. 23 became pregnant and 10 (44%) required ITP-treatment during their 

pregnancy. Conclusion: Glucocorticoids are the most common therapy for chronic ITP but 

complementary and alternative treatments already come second and less than 1/3 of the 

patients are splenectomized. This and the frequent use of complementary medicines 

94

suggests dissatisfaction with conventional therapeutic approaches. Many patients receive 

off-label therapies (rituximab, anti-D, cyclosporine are not licensed for ITP in Germany). 

There is a major need for adequate counseling and care for pregnant ITP-patients. 


Full Text: 


69. Impact of pregnancy on the course of immune thrombocytopenic purpura: An 

observational study on 44 cases 

Author(s): Baili L., Khellaf M., Languille L., Bierling P., Godeau B., Michel M. 



Abstract: Backgound: Adult's immune thrombocytopenic purpura (ITP), now referred as 

immune thrombocytopenia, is an autoimmune disease affecting preferentially women of 

child-bearing age. The risk of relapse or worsening of the disease during pregnancy in 

women with a previous history of ITP or followed for a chronic ITP is not well known and 

the monitoring of such patients is therefore not consensual. In order to better asses the 

impact of pregnancy on ITP' course and natural history, a study was initiated at the 

national referral center for adult's immune cytopenias at Creteil, France. Patients and 

Methods: This was an observational single center study. To be included into the study, all 

women had to fulfill the following inclusion criteria: 1) A previous history of definite ITP 

outside pregnancy with a platelet count < 50x10 9 /L at time of diagnosis and 2) Occurrence 

of at least one pregnancy within 10 years after ITP diagnosis. Patients diagnosed with 

secondary ITP (lupus-associated or other) or in whom ITP was diagnosed during a previous 

pregnancy could not be included. All available clinical and biological ITP-related data 

available before, during and after each pregnancy were extensively reviewed and 

analyzed. Results: Data on 44 pregnancies in 33 women (mean age: 25 +/- 7 years) were 

analyzed. The mean delay between ITP diagnosis and first pregnancy was 52 +/- 19,8 

months. At the beginning of pregnancy, ITP was considered active (i.e platelet count 

100 x10 9 /L) in 75% of the cases, either off 

therapy (82%) or on treatment (18% of the cases). In total, the platelet count remained 

stable during pregnancy In 25/44 of the cases (57%) without the need of any treatment 

except for one patient who received corticosteroids for an associated autoimmune 

hemolytic anemia diagnosed during pregnancy (Evans' syndrome). A slight decrease in the 

platelet count (between 50 and 100x10 9 /L) was observed in 12 cases (27%), 6 of which 

occurred at the end of pregnancy. In nine of these cases, patients were given a short 

course of corticosteroids in preparation for delivery. Lastly, a decrease of the platelet 

count below 50x10 9 /L was observed in only 7 of the 44 pregnancies (16%). In 6 of these 7 

cases, patients were given corticosteroids, either alone (n=2) or in combination with 

intravenous immunoglobulin (n=4 cases); one patient was also given a platelet 

transfusion. No severe bleeding episode (mucosal bleeding or any hemorrhage) occurred 

in any of these cases prior to, during or after delivery. A miscarriage occurred in 6 of the 

44 pregnancies (13.5%), a C-section was performed in 18% of the cases which is the usual 

average rate in France. In total, a treatment for ITP had been considered useful in 15 

pregnancies (34%) mainly at the end of the third trimester. The mean platelet count at 

time of delivery was 107 +/- 17 x10 9 /L, None of the patients had a relapse or a significant 

decrease of the platelet count within 6 months after delivery except for a one patient who 

presented with a severe (platelet count < 20 x10 9 /L) and symptomatic (cutaneous and 

mucosal bleeding) thrombocytopenia on day 2 after delivery. Conclusion: Based on these 

preliminary data, pregnancy does not seem to have a negative impact on the course of the 

95

disease in women with chronic non-refractory ITP nor to increase the risk of relapse in 

those with a previous history of ITP. A significant decrease of the platelet count may occur 

in about 15% of the cases, mainly during the third trimester. In women with a platelet 

count between 50 and 100 x 109/L at term, a short course of treatment could be indicated 

in preparation for delivery and especially if an epidural analgesia is planned. 


Full Text: 


70. Intracranial hemorrhage in alloimmune thrombocytopenia: Stratified 

management to prevent recurrence in the subsequent affected fetus 

Author(s): Bussel J.B., Wissert M., Tsaur F.W., Hung C., Primiani A. 



Abstract: Introduction: Fetal and neonatal alloimmune thrombocytopenia (AIT) result 

from parental platelet-specific antigen incompatibility combined with maternal 

sensitization. AIT is the most common cause of severe thrombocytopenia and intracranial 

hemorrhage (ICH) in term newborns; if ICH occurs in 1 child then the next affected sibling 

has a > 90% chance of developing an ICH. Prevention of recurrent ICH is the primary goal 

of antenatal management of AIT. Methods: Thirty-three women with 37 separate 

pregnancies were enrolled in 2 consecutive studies of antenatal management of AIT. All 

patients had a previous child who had suffered an ICH. They were subdivided into 3 

groups (Extremely High Risk (EHR), Very High Risk (VHR) and High Risk (HR)) based on the 

timing of that child's ICH. Therapy was stratified according to the timing of the sibling ICH. 

The table below lists risk stratification, treatment and outcomes for each treatment arm. 

In all arms, if fetal blood sampling (FBS) showed a platelet count < 30,000/mL 3 or if FBS 

was not performed, therapy was intensified with additional prednisone and/or 

intravenous IVIG. Results: The mean, on-therapy fetal platelet count was greater than the 

previous sibling birth platelet count (BPC) in all arms. The first EHR fetus, whose mother 

received IVIG 1g/kg/wk and prednisone 1mg/kg/d beginning at week 12, suffered an ICH 

at 19 weeks gestation and died. The EHR protocol was changed to IVIG 2g/kg/wk. None of 

the 7 other EHR fetuses had an ICH, and all had BPC > 50,000/mL 3 . Two patients in the 

VHR group had ICHs, but both occurred at BPC > 100,000/mL 3 . One was a Grade I (of IV) 

ICH; the other occurred in a 24-week-old premature infant. Fourteen of the 17 VHR 

fetuses had BPC > 50,000/mL 3 . Within the HR group, 2 fetuses (therapy started at 20-24 

weeks), suffered an ICH. One patient should have been treated in the VHR arm, but could 

not receive optimal treatment due to late referral. The other ICH was Grade I, although 

the BPC was low. All HR fetuses, except for 3 receiving IVIG 1g/kg/wk starting at 20-24 

weeks, had BPC > 50,000/mL 3 . Major complications of the study were FBS-related: 1 case 

of fetal tachycardia and 8 cases of fetal bradycardia; 3 cases lead to emergent cesarean 

section, one a result of hemorrhaging from the needle insertion site. Discussion: Fetuses 

of AIT-affected pregnancies with ICH in a previous affected sibling are at very high risk for 

ICH. The results of this study demonstrate the success of risk-tailored treatment in 

prevention of recurrent ICH. Although all or almost all 37 of the fetuses in this study would 

have developed a recurrent ICH, there were only 5 recurrent ICHs and only 2 of 5 occurred 

due to failure of therapy. Treatment should be stratified based on the timing of the sibling 

ICH: the highest risk is second trimester antenatal hemorrhage followed by third trimester 

followed by perinatal. See the table below for recommended treatments for each group. 

Since complications due to FBS continued to be substantial, FBS should be avoided until 

after 32 weeks at which time urgent delivery could be performed if a complication 

occurred. The intensification of treatment at fixed gestational ages rather than relying on 

96

the results of FBS further minimizes the need for early FBS. Risk Stratification, Treatment, 

Outcome and Recommendations (Table prsented) ICH, intracranial hemorrhagt; IVIG, 

intravenous immunoglobulin; Pred, prednisone; BPC, birth platelet count; FPC, fetal 

platelet count; FBS, fetal blood sampling. 


Full Text: 


71. Therapeutic plasmapheresis and intravenous immunoglobulin as a treatment 

modality in a 45 year old pregnant female with refractory idiopathic thrombocytopenic 

purpura: A case report 

Author(s): Giovanniello D.S., Chiofolo J.T., Grima K. 

Citation: Transfusion, September 2009, vol./is. 49/(77A), 0041-1132 (September 2009) 


Abstract: Background: Idiopathic thrombocytopenic purpura (ITP) is a clinical syndrome in 

which a decreased number of circulating platelets manifests as a bleeding tendency, easy 

bruising, or extravasation of blood from capillaries into skin and mucous membranes. In 

patients with ITP, platelets are coated with autoantibodies (usually IgG) to platelet 

membrane antigens, resulting in splenic sequestration and destruction. The resulting 

shortened life span of platelets in circulation results in a decreased platelet count. The 

platelet antibodies and ensuing reduction in platelet count in pregnancy can increase 

morbidity and mortality secondary to maternal hemorrhage at time of birth and can result 

in neonatal thrombocytopenia, secondary to maternal antibodies crossing the placenta. 

Neonatal thrombocytopenia places the infant at risk for intracranial or visceral 

hemorrhage. Treatment options in ITP patients usually include corticosteroids and 

intravenous immunoglobulin (IVIG), with splenectomy in more chronic disease conditions. 

Therapeutic plasmapheresis has not been viewed as beneficial for use in ITP patients, 

secondary to the rapidly equilibrating interstitial antibodies present in this disease. The 

addition of IVIG may prevent this equilibrating rebound phenomenon. There are several 

case reports which support this combination and one small trial showing that the 

combination of plasmapheresis and steroids was beneficial in decreasing relapse rate 

(Transfusion 1981;21:291- 8), suggesting that the addition of plasmapheresis may provide 

some benefit. Case Report: We present a case report of a 45 year old, 10 week pregnant, 

female with a history of two failed pregnancies, at least one of which failed at 14 weeks 

gestation, and ITP refractory to treatment with high doses of prednisone and IVIG. The 

admission platelet count was 16,000/?L. Within 24 hours, the platelet count dropped to 

2,000/?L. The patient was treated with a combination of three plasmapheresis procedures 

where 3 liters of plasma were removed and replaced with 2 liters 5% albumin and 1 liter 

of FFP, followed by 80 mg/kg IVIG weekly. The patient's platelet count subsequently rose 

to 41,000/?L upon discharge. The platelet count remained stable for the remainder of the 

pregnancy (40-50,000/?L) while being maintained on prednisone 80 mg and IVIG 80 mg/kg 

weekly at home. She delivered a normal baby with a normal platelet count of 272,000/?L 

at 31 weeks gestation by Cesarean section, prematurely secondary to preterm premature 

rupture of membranes (PPROM). Conclusion: Patients with refractory ITP may benefit 

from a combination of therapeutic plasmapheresis and IVIG. In pregnancy, this reduces 

the risk of hemorrhage to both the mother and infant. 


Full Text: 


97



if required. 

72. Successful treatment of a pregnant woman with active systemic lupus 

erythematosus (SLE) and secondary idiopathic thrombocytopenic purpura (ITP) after 3 

sessions of plasma exchange: A case report 

Author(s): Hussein E.A., Sameeh I.A. 

Citation: Transfusion, September 2009, vol./is. 49/(76A-77A), 0041-1132 (September 

2009) 


Abstract: Background: There is controversy about the therapeutic efficacy of plasma 

exchange (PE) in patients with active SLE. Case report: We report a case of a 26-year old 

female, pregnant at 24 weeks, presenting with pallor, vaginal bleeding, bleeding gums, 

facial rash, blurry vision, and lymphadenopathy. She was admitted to our hospital with 

pancytopenia and received packed red cells and 18 units of platelets. A diagnosis of SLE 

with secondary ITP was made based on her laboratory findings which revealed; 

leucopenia, thrombocytopenia with a platelet count of 6,000/?L, evidence of hemolysis 

with hyperbilirubinemia and a hemoglobin level of 5 gm/dl, positive antinuclear antibody, 

positive anti double- stranded- DNA antibody, positive lupus anticoagulant, false positive 

VDRL, and decreased complement levels. Direct coombs' test was negative and her LDH 

(lactate dehydrogenase) was 529 IU/L. The patient had normal coagulation, and renal 

parameters. TTP (thrombotic thrombocytopenic purpura) was ruled out when no 

schistocytes were identified manually in the peripheral blood smear. Pre-eclampsia, 

eclampsia, and HELLP (hemolysis, elevated liver enzymes and low platelet count) 

syndrome were also excluded. High doses of corticosteroids were given when her illness 

was worsening with persistent hemolysis and thrombocytopenia. Therapy included 3 daily 

intravenous pulse doses of methyl prednisolone 500 mg, followed by a daily maintenance 

dose of methyl prednisolone 40 mg. She also received cyclosporine 75 mg given twice 

daily. Plasma exchange was conducted when she was not responding to the conventional 

therapy. Rapid and excellent responses were achieved when 3 PE sessions were carried 

out in combination with the previous therapy. Sessions were performed on alternate days 

with COBE Gambro machine using albumin and exchanging one plasma volume per 

session. No active hemolysis was noted and her facial rash resolved. The patient improved 

clinically, her platelet count rose to 130,000/?L and her antibody titer improved. A 

maintenance dose of steroids was prescribed after the sessions, and the dose was 

gradually reduced. She is on low dose of oral steroids (10 mg) and remains in good 

condition with no signs of hemolysis and with a healthy living fetus. Conclusion: Based on 

our case report, Plasma exchange initiated early in combination with steroids might be 

beneficial in some patients with therapy resistant active SLE. 


Full Text: 




if required. 

73. Pregnancy-related complications in women with rare production-defect 

thrombocytopenias 

Author(s): Myers B., Elliott D., Pavord S. 

98

Citation: Journal of Thrombosis and Haemostasis, July 2009, vol./is. 7/S2(886), 1538-7933 

(July 2009) 


Abstract: Thrombocytopenia in pregnancy is usually mild and related to increased platelet 

consumption rather than production defects. The latter are rare and include hereditary 

and acquired thrombocytope-nias, often mistaken for ITP. There is little information on 

pregnancy, delivery management and neonatal outcome in these conditions. A 

retrospective survey was performed evaluating pregnancy and delivery management in 

women with rare platelet production defects. 13 mothers had 32 pregnancies, (18 live 

births). The cases included women with May-Hegglin anomaly (3), other hereditary 

macrothrombocytopenias (3), TAR syndrome (4) and one each of Fanconi's anaemia, 

hypoplastic anaemia & sideroblastic anaemia. Data were collected on platelet count in 

pregnancy, antenatal complications, management of delivery, neonatal platelet count, 

and post-partum bleeding. Platelet count at booking was 16-120 (mean 56), and mean 

platelet count at delivery was 32 x 109/L (range 13-70). There were 13 early miscarriages 

(44%) at 6-12 weeks, one termination at 20 weeks (fetus with TAR syndrome) and one 

case each of: recurrent antenatal bleeding, pre-eclampsia and IUGR requiring delivery at 

31 weeks. Four babies were thrombocytopenic, range (27-49). There were no neonatal 

bleeds. Four mothers had been initially diagnosed with ITP and treated with 

prednisolone/IVIG with no platelet response in 3. There were 12 vaginal deliveries. 

Platelets were given prophylactically in 7 cases, pre-caesarean section or forceps delivery, 

and none required as an emergency. Three women had post-partum haemorrhage 

(16.6%). In conclusion, although a small group, bleeding and miscarriage rate appeared 

increased in this cohort compared to local miscarriage (15%) and PPH (5%) rates. Large 

multi-centre studies are required to assess risks and optimal management in this rare and 

heterogeneous group. 


Full Text: 


74. Maternal deaths due to acquired thrombotic thrombocytopenic purpura (ttp) in 

london, england 2003-7 

Author(s): Thomas-Dewing R.R., Lucas S.B., Hunt B.J. 

Citation: Journal of Thrombosis and Haemostasis, July 2009, vol./is. 7/S2(874), 1538-7933 

(July 2009) 


Abstract: Introduction: TTP is a life threatening disorder more common in women and 

occurs in pregnancy. Method: We retrospectively reviewed all maternal deaths due to TTP 

in London, confirmed on post mortem examination from 2003 to 2007. The aim of this 

review was to identify the mode of death, why they died and identify any preventative 

measures that could be taken to prevent future deaths. Results: There were three 

maternal deaths in women aged 29, 31 and 35 years and parity 1, 2 and 3 respectively 

with no previous complicated pregnancies or TTP, but one had systemic lupus 

erythematosus (SLE). Two presented post partum and the third at 24 weeks of gestation. 

The first patient was diagnosed with TTP at presentation, but died before treatment was 

initiated; the second had a late diagnosis initially thought to have ITP and then HELLP 

(haemolysis, elevated liver enzymes, low platelets) syndrome and died while awaiting 

transfer to another hospital for plasmapheresis; the third patient was diagnosed with SLE 

related complications and a diagnosis of TTP was made post mortem. All three patients 

died of sudden cardiac arrest within 1, 5 and 2 days of presentation respectively. Post 

99

mortem findings revealed all three patients died with intramyocardial microvascular 

thrombosis, the thrombi being characteristically platelet rich (CD61 +, fibrin-). Von 

Willebrand factor cleaving protease level (vwf-cp) was not measured in the first, was 0% in 

the second and 5% in the third (normal range 66% to 126%) at presentation. Discussion: 

This study shows that platelet thrombi in the coronary microvasculature are a significant 

cause of early sudden death in TTP in pregnancy, and a reminder of the need to institute 

plasmapheresis as soon as possible. If the diagnosis is in doubt especially in differentiating 

between the thrombotic microangiopathies of pregnancy, vwf- cp levels should be 

collected for measurement, but results not awaited before instituting plasmapheresis. 


Full Text: 


75. Gestational thrombocytopenia, is it not simply physiological hypersplenism? 

Author(s): Bulvik S., Niven M.J. 

Citation: Haematologica, June 2009, vol./is. 94/(526), 0390-6078 (June 2009) 


Abstract: Background. Thrombocytopenia is an ominous sign during pregnancy. Although 

one of the main reason for it is gestational thrombocytopenia, a benign condition 

occurring in 8% of all pregnancies and accounting for more than 70% of cases of 

thrombocytopenia in pregnancy, there is no pathonomonic sign for it and the diagnosis is 

by exclusion of other, sometimes emergent, causes of thrombocytopenia, such as HELLP 

syndrome, DIC, Pre Eclampsia, TTP, ITP etc. Aims. To establish a simple test for the 

diagnosis of gestational thrombocytopenia. Design and Methods. Nineteen pregnant 

women with an eventual diagnosis of gestational thrombocytopenia were investigated 

including standard physical examination, blood film, coagulation testing, liver function 

tests and abdominal ultrasonography. Results. Of the 19 women, 16 had splenomegaly on 

both physical examination and ultrasound. In the remaining 3 spleen size was at the upper 

limit of normal on ultrasonography. The reason for this was physiological gestational 

splenomegaly, which resolved immediately after the pregnancy. Conclusion. We suggest 

that in pregnant women with asymptomatic thrombocytopenia a finding of physiological 

splenomegaly strongly suggests the diagnosis of gestational thrombocytopenia. Larger 

studies are needed to confirm this hypothesis that gestational thrombocytopenia is simply 

due to hypersplenism secondary to the pregnancy. 


Full Text: 



76. Treatment of ttp in pregnancy with therapeutic plasma exchange 

Author(s): Nelson G., Raife T., Erikson Y. 

Citation: Journal of Clinical Apheresis, 2009, vol./is. 24/2(89), 0733-2459 (2009) 


Abstract: History: The patient is a G2P1 35 year old pregnant female with a history of 

thrombocytopenic purpura (TTP). During her first pregnancy in 2003 she presented with 

thrombocytopenia, discovered on a routine CBC. She was initially treated with prednisone 

for presumed ITP, and underwent emergent cesarean section. Her thrombocytopenia 

100

progressed and she was eventually diagnosed with TTP. She was successfully treated with 

a prolonged course of therapeutic plasma exchange (TPE). In 2005 she had a recurrent 

episode of TTP in which she presented with fever and bruising. There were no known 

stimulating factors. She was again successfully treated with TPE. Her ADAMTS13 level was 

subsequently found to be undetectable, and she had a high level of ADAMTS13 inhibitor. 

During her second pregnancy in 2008, close laboratory monitoring revealed a gradual 

decrease in platelet counts. At 26 weeks gestation, she presented with bruising, 

thrombocytopenia, and elevated LDH. Severe preeclamptic toxemia with HELLP 

(hemolysis, elevated liver enzymes, and lowered platelets) syndrome was ruled out due to 

absence of hypertension and AST/ALT and creatinine levels within normal range. Her 

pregnancy was otherwise uncomplicated. Methods: TPE was performed using the Cobe 

Spectra. The volume removed with each TPE ranged from 3200-4000mL. Replacement 

fluid consisted of a combination of 5% Albumin (volume ranged from 250-750mLs), 

Normal Saline (volume ranged from 500-1000mLs), and cryo-poor plasma (volume ranged 

from 1600-2600mLs). All TPE were maintained at a fluid balance of 95%. During the course 

of TPE, the patient received steroid treatments. Fetal monitoring was performed 

throughout all exchanges. Results: TPE treatments spanned Jan. 7th -Feb 8th 2008. Daily 

TPE was initially performed for eight days. Jan 14th 2008 patient was discharged with plan 

of every other day TPE. On Jan 20th the patient was re-admitted due to a decrease in 

platelet count. Daily TPE resumed. On Jan 30th TPE tapered to a M-WF schedule. The 

infant was delivered Feb 4th 2008 due to fetal distress. The patient received two TPEs 

following delivery. The infant was alive and well at completion of TTP treatments. 

Discussion: The TPE treatment in conjunction with steroid treatment and close fetal 

monitoring maintained the pregnancy through week 30 1/7. Following delivery, the TTP 

resolved. This case demonstrates that with appropriate obstetrical care, TPE can 

successfully support a TTP patient in the 3rd trimester of pregnancy. 


77. Autoimmune thrombocitopenic purpura in pregnancy 

Author(s): Christova R., Lisichkov T., Chernev T. 

Citation: Akusherstvo i ginekologiia, 2009, vol./is. 48/6(42-46), 0324-0959 (2009) 


Abstract: The author deals with haematologists' and obstetricians' current views on 

acquired ATP in children and adults, characterised by a transient, acute or chronic 

decrease in platelets count (


78. Therapeutic approach in pregnant women with an autoimmune 

thrombocytopenic purpura 

Author(s): Christova R., Lisichkov T., Chernev T. 

Citation: Akusherstvo i ginekologiia, 2009, vol./is. 48/6(53-54), 0324-0959 (2009) 


Abstract: The case presented herein aim to update the existing information about the 

common diagnostic problems and therapeutic approach in pregnant women that have 

autoimmune thrombocytopenic purpura (ATP). 


79. Uneventful epidural analgesia in a patient with severe thrombocytopenia 

Author(s): Ibrahim S.M., Elgazali M.S. 

Citation: Middle East Journal of Anesthesiology, 2009, vol./is. 20/2(291-294), 0544-0440 

(2009) 


Abstract: Epidural analgesia is the most effective method for analgesia in labor. It has, 

however, contraindications and carries many serious side effects. Though coagulopathy is 

an absolute contraindication for epidural and axial blocks, yet there are no absolute limits 

for platelet counts that stand in the way of providing epidural analgesia. In a patient who 

is writhing in pain due to severe uterine contractions, and in whom there exists a recent 

normal platelet screening and no history of bleeding disorders, it is internationally 

acceptable between anesthetists to provide epidural analgesia without waiting for a new 

platelet screening. 


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103

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104

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