Idiopathic Thrombocytopenic Purpura (ITP) - Pathology

Idiopathic Thrombocytopenic Purpura 1
Idiopathic
Thrombocytopenic
Purpura (ITP)
Roger S. Riley, M.D., Ph.D.
April, 2006
Feature
Synonyms
Epidemiology
Etiology &
Pathogenesis
Disease Facts
ITP, primary immune thrombocytopenic purpura, autoimmune thrombocytopenic purpura.
True incidence is unknown, since individuals with mild disease may be asymptomatic
and undiagnosed. In the United States, symptomatic disease occurs in about 70
adults/1,000,000 and 50 children/1,000,000.
Autoimmune disease, with anti-platelet antibody formation (usually specific for the
platelet GPIIbIIIa receptor) and peripheral platelet destruction. Acute ITP usually occurs
in children, follows an acute viral infection or recent live virus immunization, and
usually undergoes a spontaneous remission within two months. Chronic ITP is more
common in adults, shows an insidious presentation, and lasts > 6 months. The pathogenesis
is complex and multifactorial, including a failure of self-antigen recognition and
tolerance, altered cytokine secretion, impaired megakarypoiesis, and impaired cellmediated
cytotoxicity.
Clinical
Presentation
Symptomatic individuals present with “platelet-type” bleeding problems. These
include non-palpable petechiae, purpura, epistaxis, gingival bleeding, menorrhagia,
and easy bruising. GI bleeding, hematuria, retinal hemorrhage, and
even intracranial hemorrhage can occur in severe cases. Splenomegaly is unusual.
Differential
Diagnosis
All causes of thrombocytopenia must be excluded. The major considerations
include pseudothrombocytopenia, DIC, viral infections (especially HIV and
EBV), TTP, and drug-induced thrombocytopenia (heparin, alcohol, sulfinamides,
quinine, quinidine). Other disease in the differential include pregnancyassociated
thrombocytopenia, autoimmune disease (especially lupus erythrmatous),
other infections, liver disease, hematologic and other malignancies,
transfusion reaction.
Laboratory
Features
Laboratory studies are more valuable in the exclusion of other diseases than in
providing definitive evidence of ITP. Variable thrombocytopenia with a normal
white blood count and erythrocytic indices (in the absence of severe hemorrhage).
Peripheral blood smear examination reveals thrombocytopenia with
normal leukocytic and erythrocytic morphology. Coagulation assays are within
normal limits. Bone marrow evaluation reveals normal to increased megakaryocytes
with normal morphology. Assays for platelet-associated immunoglobulin
by ELISA or flow cytometry may be positive, but these assays are presently
considered unreliable. Pseudothrombocytopenia must be excluded by peripheral
smear examination for platelet clumping. The exclusion of other causes of
thrombocytopenia should include other laboratory assays, especially a CBC, D-
dimer and FDP assay, LDH, viral serology (especially for HIV), anti-nuclear antibody,
rheumatoid factor studies, and ESR, liver function studies, and pregnancy
test.

Idiopathic Thrombocytopenic Purpura 2
Feature
Treatment
Disease Facts
Supportive care, including platelet transfusions, must be provided until remission
occurs or treatment is effective. No specific treatment is usually provided
for children with platelet counts >30,000/µL or adults with >50,000 platelets/
µL. Intravenous immunoglobulin (IVIG, IV Rh immune globulin, IV anti-Rh(D)
and corticosteroids are the first line of therapy for patients with severe thrombocytopenia.
Rituximab is often used in patients with refractory ITP.
References
Aledort LM et al. Prospective
screening of 205 patients with
ITP, including diagnosis, serological
markers, and the relationship
between platelet
counts, endogenous thrombopoietin,
and circulating antithrombopoietin
antibodies.
Am J Hematol 76(3):205-213,
2004.
Andersson PO, Wadenvik H.
Chronic idiopathic thrombocytopenic
purpura (ITP): molecular
mechanisms and implications
for therapy. Expert
Rev Mol Med 6(24):1-17,
2004.
Blackwell J, Goolsby MJ. Diagnosis
and treatment of idiopathic
thrombocytopenic purpura.
J Am Acad Nurse Pract
15(6):244-245, 2003.
Blanchette VS, Carcao M.
Childhood acute immune
thrombocytopenic purpura: 20
years later. Semin Thromb
Hemost 29(6):605-617, 2003.
Cines DB, Bussel JB. How I
treat idiopathic thrombocytopenic
purpura (ITP). Blood
106(7):2244-2251, 2005.
Cines DB, McMillan R. Management
of adult idiopathic
thrombocytopenic purpura.
Annu Rev Med 56:425-442,
2005.
Drachman JG. Inherited
thrombocytopenia: when a
low platelet count does not
mean ITP. Blood 103(2):
390-398, 2004.
George JN, Vesely SK. Immune
thrombocytopenic
purpura--let the treatment fit
the patient. N Engl J Med
349(9):903-905, 2003.
Introna M, Golay J, Barbui T.
Rituximab: a new therapeutic
tool for primary immune
thrombocytopenic purpura?
Haematologica 88(5):
482-484, 2003.
Kojouri K, George JN. Recent
advances in the treatment of
chronic refractory immune
thrombocytopenic purpura.
Int J Hematol 81(2):119-125,
2005.
Kravitz MS, Shoenfeld Y.
Thrombocytopenic conditionsautoimmunity
and hypercoagulability:
commonalities and
differences in ITP, TTP, HIT,
and APS. Am J Hematol
80(3):232-242, 2005.
Kumar M et al. Treatment,
outcome, and cost of care in
children with idiopathic
thrombocytopenic purpura.
Am J Hematol 78(3):181-187,
2005.
Kuwana M et al. Initial laboratory
findings useful for predicting
the diagnosis of idiopathic
thrombocytopenic purpura.
Am J Med118(9):1026-
1033, 2005.
McMillan R. Antiplatelet antibodies
in chronic adult immune
thrombocytopenic purpura:
assays and epitopes. J
Pediatr Hematol Oncol 25
Suppl 1:S57-61, 2003.
Munson BL. Myths and facts
...about idiopathic thrombocytopenic
purpura. Nursing
34(11):76, 2004.
Provan D, Newland A. Fifty
years of idiopathic thrombocytopenic
purpura (ITP): management
of refractory itp in
adults. Br J Haematol
118(4):933-944, 2002.
Rodeghiero F. Idiopathic
thrombocytopenic purpura: an
old disease revisited in the era
of evidence-based medicine.
Haematologica 88(10):1081-
1087, 2003.
Sandler SG. Review: immune
thrombocytopenic purpura: an
update for immunohematologists.
Immunohematol
20(2):112-117, 2004.
Shirahata A, et al. Consensus
guideline for diagnosis and
treatment of childhood idiopathic
thrombocytopenic purpura.
Int J Hematol 83(1):29-
38, 2006.
Stasi R, Provan D. Management
of immune thrombocytopenic
purpura in adults.
Mayo Clin Proc 79(4):504-
522, 2004.
Terrell DR et al. The incidence
of thrombotic thrombocytopenic
purpura-hemolytic
uremic syndrome: all patients,
idiopathic patients, and
patients with severe ADAMTS-
13 deficiency. J Thromb Haemost
3(7):1432-1436.
Vianelli N et al. Efficacy and
safety of splenectomy in immune
thrombocytopenic purpura:
long-term results of 402
cases. Haematologica
90(1):72-77, 2005.

Idiopathic Thrombocytopenic Purpura 3
References
Yildirmak Y et al. Antiplatelet
antibodies and their correlation
with clinical findings in
childhood immune thrombocytopenic
purpura. Acta Haematol
113(2):109-112, 2005.
Zhou B, Zhao H, Yang RC,
Han ZC. Multi-dysfunctional
pathophysiology in ITP. Crit
Rev Oncol Hematol
54(2):107-116, 2005.