Sickle Cell Disease and Acute Chest

Morning Report
4/18/12
Dr. Dudley
Jen McDonnell

MKSAP
A 19-year 19 year-old old black man is evaluated in the emergency
department for a 2-day 2 day history of pain in the upper and
lower extremities and back. His medical history
includes episodes of achy pain in his extremities and
back, but this is the first time his pain was severe
enough to seek medical attention. Medical history is
also remarkable for anemia of unknown cause. Family
history is positive for anemia. Other than poor exercise
tolerance, the patient has no other medical problems,
no allergies, and takes no medications.

MKSAP
On physical examination, there are mildly icteric
sclerae. sclerae.
Temperature is 37.2 °C C (99.0 °F), F), blood
pressure is 126/62 mm Hg, pulse rate is
112/min, and respiration rate is 18/min; BMI is
22. There is no splenomegaly
or hepatomegaly
on abdominal examination.

Laboratory studies:
Hemoglobin
Leukocyte count
MKSAP
10.2 g/dL
(102 g/L)
109/L)
8600/µL 8600/ L (8.6 ×
Mean corpuscular volume
70 fL
Total bilirubin
5.7 mg/dL mg/ dL (97.5 µmol/L) mol/L)
Direct bilirubin
0.3 mg/dL mg/ dL (5.1 µmol/L) mol/L)
The peripheral blood smear shows rare sickled
erythrocytes and target cells.

MKSAP
Hemoglobin electrophoresis:
Hemoglobin S
Hemoglobin F
Hemoglobin A
Hemoglobin A2 A
67% (0%)
3% (0%-2%) (0% 2%)
25% (94.8%-97.8%)
(94.8% 97.8%)
5% (2.2%-3.2%) (2.2% 3.2%)

1.
2.
3.
4.
MKSAP
Which of the following is the most likely
diagnosis?
Sickle cell trait
Sβ+ + thalassemia
Hemoglobin SC disease
Hemoglobin S with hereditary persistence of
fetal hemoglobin

1.
2.
3.
4.
Which of the following is the most likely diagnosis?
Sickle Cell Trait
S+ Thal
SC Disease
Hemoglobin S with
hereditary persistence of HF
25% 25% 25% 25%
1 2 3 4

MKSAP
This patient has Sβ+ + thalassemia, thalassemia,
characterized by a hemoglobin
S level that is greater than 60%, with an elevated hemoglobin A2
level and mild microcytosis. microcytosis.
These patients have painful crises,
but to a lesser extent than patients homozygous for hemoglobin
S. Patients with Sβ+ + thalassemia
have target cells and few or no
sickled
erythrocytes on the peripheral blood smear. Patients with
sickle cell trait (AS), who are often confused with patients with with
Sβ+ + thalassemia, thalassemia,
have a hemoglobin S level that is less than 50%
and a hemoglobin A level that is correspondingly greater than
50%. Patients with the sickle cell trait also have normal-sized
normal sized
erythrocytes. Patients with hemoglobin SC disease have painful
crises in addition to an approximately 50:50 ratio of hemoglobin
S to hemoglobin C on electrophoresis.

MKSAP
On physical examination, there are mildly icteric
sclerae. sclerae.
Temperature is 37.2 °C C (99.0 °F), F), blood
pressure is 126/62 mm Hg, pulse rate is
112/min, and respiration rate is 18/min; BMI is
22. There is no splenomegaly
or hepatomegaly
on abdominal examination.

Chief Complaint
23 year old male with sickle cell disease coming
to the ER with upper and lower extremity pain.

HPI
Pain in upper and lower extremities for the past
week. Pain sensation and distribution is typical
of VOC for patient. Started home pain regimen
3 days prior to admission but unable to control
pain. No fevers, no chills, no chest pain, no
SOB, abdominal pain, constipation, diarrhea.
Patient has had a chronic tibial
ulcer-thinks may
be draining slightly more, but no other changes
to ulcer.

Key Items in Sickle Cell History
Current symptoms
Paying close attention to
signs of infection, ACS,
abdominal pathology
Past history:
Previous ACS, other
complications
Recent
hospitalizations/complications
Frequency of complications
History of stroke
Complications from
SCD
Pulmonary HTN
Hemochromatosis
Renal dysfunction
AVN
Medical Regimen
Home meds
Previous hospitalization
pain meds/PCA

PMH:
Hg SS disease
Pulmonary HTN-mild
History of CVA-age 17, no
residual deficits
RLE DVT 1 year ago
AVN L hip
ACS X 3
Acute cholecystitis
Migraines
Allergies: NKDA
PMH
Medications:
Morphine IR 15mg PO Q3-4h
PRN
Morphine SR 30mg BID
Hydroxyurea 1500mg daily
Folic acid 1mg daily
Social History: Lives with
girlfriend, 3 y/o daughter,
grandparents. Tob: 3 cigs/day
ETOH: rare +marijuana-last use 3
weeks ago
Family History: Sister with sickle
cell disease, died at the age of 18
months.

Physical Exam
T 36.2 HR 76 BP 124/60 RR 18 SPO2: 100% 2L NC (98% RA)
Constitutional: He is oriented and conversant, appears uncomfortable
HENT: Eyes: Conjunctivae normal, EOMI. Pupils are equal, round, and
reactive to light. Neck supple.
Cardiovascular: Regular rate and regular rhythm, S1, S2 present, S2 slightly
pronounced, no murmurs, rubs, or gallops. No lift of heave
Pulmonary: Effort normal and breath sounds normal. No respiratory distress.
No wheezes. No rales.
Abdominal: Bowel sounds are normal. No distension. Soft. No tenderness.
No rebound and no guarding.
Musculoskeletal: Diffusely painful to light touch on all 4 extremities
Neurological: He is alert and oriented. No cranial nerve deficit. Coordination
normal.
Skin: open right tibial ulcer 7cm X 8cm X 4cm

10.8
144
3.7
11.4
32.4
107
27
515
N 48 L 34 M 11 E5 reactive
lymph 1 myelocyte 1
4
Initial Labs
0.5
Reticulocyte count:7.5% (RPI
2.7)
98
8.4
7.7 3.8
1.4
60 29
84

CXR
FINDINGS:
Mild cardiomegaly, unchanged. Basilar streaking
opacities compatible with scarring or
subsegmental atelectasis, not significantly
changed.
IMPRESSION:
No evidence of infection.

Before starting therapy for VOC, your medical
student asks, what else could cause pain in
sickle cell patient?
Acute chest syndrome
Cholecystitis
Right Upper Quadrant Syndrome
Priapism
Splenic
sequestration
Avascular
necrosis
Vertebral body collapse

What will be your therapy for VOC?

Loading dose
Yes
Relief?
No
PCA
Calculate 24 hour
Dose requirement
Reassess at 30
Minute intervals
Adjust demand interval to q15-30 minutes
2/3 dose
1/3 dose
demand
continuous
Set lockout interval to
Q5 minutes during first
2 hours (titrate dose)
Maintain relief with around
the clock dosing

Adjuvant therapies
NSAIDs
ketorolac
IV fluids
Anti-emetics Anti emetics
Anti-histamines
Anti histamines
Anxiolytics
Antidepressants, anticonvulsants, clonidine
neuropathic pain
for

Perception of Addiction

Pseudoaddiction
Concept that patients whose pain is inadequately
treated will develop characteristics frequently
attributed to pain seeking behavoir
“clock clock watching” watching
Frequent ER visits
Seeking care at multiple sites
Change in demeanor when medical personnel
present

Hospital Course
Patient admitted, placed on IVF, dilaudid PCA
On hospital day #3 05:45, patient noted to be
less responsive with the following vitals: T 36.2
HR 126 BP 87/52 RR 20 SpO2 70% RA
100% 5LNC

CXR
Moderate hypervolemia/CHF. Basilar opacities
nonspecific but could represent
pulmonary infection in the appropriate clinical
context.

21
140
6.4
98
20
Lactic acid 10.1
9.4
27.5
434
32
2.9
80
Labs
7.9
2.6
8.8
6.9 3.5
8.6
ABG: 7.28/49/139/94% on 5L NC
366 321
87
1.9/6.7

Hospital Course
Patient initially given 1L fluid bolus with follow
up BP 90/60. Patient continued to require
increased oxygen support.
RRT called: patient treated for hyperkalemia,
transferred to MICU

ACS
Definition: new pulmonary infiltrate +/-
fever, chest pain,
tachypnea, tachypnea,
cough, dyspnea, dyspnea,
wheezing
Major cause of ICU admissions and death in sickle cell
population
Incidence 10.5 per 100 patient years
Frequently develops after admission for VOC
Mortality: 9% in adults
Infections: Strep pneumo, pneumo,
E coli, Haemophilus,
Haemophilus,
legionella, legionella,
CMV,
S aureas, aureas,
chlamydia

ACS

ACS Treatment
Simple or exchange transfusion-
small studies have
not shown a difference in two, however, most
recommend use of exchange transfusion for severe
cases, those not responsive to simple transfusion
Antibiotics:
3 rd rd-4 th generation cephalosporin +
macrolide, macrolide,
or based on local resistance/risk factors. No
RCT has been done for abx, abx,
but usually given
Inhaled NO:
Current studies have shown no
improvement in outcomes

ACS Treatment
Corticosteroids: variable results in studies, not
currently conclusively beneficial
Bronchodilators: used in patients with wheezing,
airway obstruction, but some advocate using for all
patients. No well-powered trial evaluating use.
Anticoagulation: RCT, double blind trial showed
reduction in duration of pain crises, duration of
hospitalization with use of tinzaparin (LMWH)
ECMO: Option for patients who do no respond to
mechanical ventilation

Multi-organ failure syndrome
Multiple definitions, but in general development
of severe dysfunction of at least 2 major organs
(lung, kidney, liver)

What do you need to do exchange
transfusion?

Hemoglobinopathy
Hemoglobin A 8.4%
Hemoglobin A2 4.2%
Hemoglobin F
Hemoglobin S
5.4%
81.3%
evaluation

Exchange Transfusion
Rationale: Exchange sickled RBCs/HgS for
regular RBCs/HgA without increased viscosity,
fluid shifts seen with simple transfusion
Goal: Hg S

Hospital Course
Patient initially transfused 2 units pRBC
by simple
transfusion in MICU, however persistent hypoxia and
high Hg S level prompted exchange transfusion
Catheter placed and exchange transfusion initiated
repeat Hg S 36%
Within 2 days of exchange transfusion, patient’s patient s clinical
status and lab values had improved substantially
Patient transferred to floor, full recovery of renal
function, liver function

References
Paul RN et al. 2011. Acute chest syndrome: sickle cell disease. Euro J
Haematology 87 (191-207)
Hassell KL et al. 1994. Acute Multiorgan Failure Syndrome: A Potentially
Catastrophic Complication of Sever Sickle Cell Pain Episodes. Am J Med 96:
155-162.
NIH The Management of Sickle Cell Disease. NIH publication: 02-2117.
Shapiro BS et al. 1997. Sickle Cell-Related Pain: Perceptions of Medical
Practitioners. J of Pain and Symptom Management 14 (3): 168-174.
Swerdlow PS. 2006. Red Cell Exchange in Sickle Cell Disease. Am Soc
Hematology 48-53.
Gladwin MT and E Vichinsky. 2008. Pulmonary Complication s of Sickle Cell
Disase. NEJM 359:2254-65.