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Case Study
MICR 410 - Hematology
Spring, 2011
Case # 4
Jazmin Graff
Barbara Huang
Marian Navarrete
Case Summary
• Ms. Chang, a 35-year-old woman
• Complained of weakness, low grade fever, periods of
forgetfulness, and memory loss for last week or so.
• Denied any viral/bacterial illness prior to onset of
symptoms.
• + Oral contraceptives, but no other drugs.
• Large number of bruises on her extremities.
• As her condition worsen, she began to be afflicted
with frequent seizures, headaches, and dizziness.
Key Information Pointing to Diagnosis
Symptoms
•Low grade fever
•Periods of forgetfulness and memory
loss
• Seizures, headaches, and dizziness
•Bruises on extremities
Sinificant Laboratory Findings
•Peripheral Smear:
–Schistocytes and
polychromasia
Table 1: Laboratory Results
Test
Result
Normal Range
Hemoglobin
6.0 g/dL
12.3-15.3 g/dL
Hematocrit
0.18 L/L
0.38-0.46 L/L
White Blood Cells
8.9 x 109/L
4.1-10.9x109/L
Platelet
31 x109/L
150-450x109/L
Reticulocyte
2.5%
Table 2: Results of urinalysis
Protein
2+
Blood
+
* Renal insufficiencies
Diagnosis: MAHA
• Significant lab results confirmed
the presence of hematuria,
decreased hemoglobin, and
thrombocytopenia, but most
importantly, the presence of
Schistocytes. All of these
findings are consistent with a
hemolytic episode associated
with:
– Micriangyophatic
Hemolytic Anemia
(MAHA).
– Cause of MAHA: thrombotic
thrombocytopenic purpura
(TTP)
Pathophysiology of MAHA
• MAHA is a microangiphatic subgroup of hemolytic anemia and is
caused by a mechanical disruption of the red blood cell membrane
in circulation, leading to intravascular hemolysis.
• TTP can be categorized into 2 major forms:
– Hereditary: Often seen in children, and caused by mutations of
ADAMTS13 gene
– Acquired: Mainly seen in adults, may be idiopathic or
nonidiopathic.
• Idiopathic: results from autoantibodies that inhibit
ADAMTS13 function
• Nonidopathic: TTP is secondary to other conditions such as
hematopoeitic stem cell transplantation, certain drugs,
infections, other autoimmune diseases, cancers, and so on.
Pathogenesis of idiopathic TTP caused by ADAMTS13 deficiency
Multimeric von Willebrand factor (VWF)
adheres to endothelial cells or to connective
tissue in the vessel wall.
Platelets adhere to the VWF. In flowing blood, VWF in the platelet-rich
thrombus is stretched and cleaved by the protease ADAMTS13, limiting
thrombus growth. If ADAMTS13 is absent, VWF-dependent platelet
accumulation continues, eventually causing microvascular thrombosis
and TTP.
*Intravascular Hemolysis
is also associated with
the presence of
Schistocytes
Renal Disease
Burr Cells
Liver Disease
Burns
Morphology :
Fragmented
Cells
Possible Pathology
Schistocyte
Prosthetic Heart Valve
Disseminated
Intravascular
Coagulation
Microangiopathic
Hemolytic Anemia
Thrombotic
Thrombocytopenic
Purpura
Clostridial Infections
Hemolytic Uremic
Syndrome
G6PD Deficiency
Helmet Cells
Pulmonary Emboli
Microangiopathic Hemolytic Anemia (MAHA)
Diagnostic Tests
•
Tests that can identify MAHA should be performed when a hemolytic episode is
suspected or has been determined.
–
–
–
–
Repeat complete CBC and calculate all parameters
Lactate dehydrogenase (LDH), haptoglobin, total bilirubin
Direct Coombs (DAT)
Repeat urinalysis tests (Dipstick Test) including differential values
• Color, clarity
• Leukocyte, WBC, RBC
• Nitrite, urobilinogen, glucose, and bilirubin
•
Tests to identify TTP include:
– Patient history and type of bleeding
– There is currently no specific routine test to confirm the diagnnosis of TTP, instead the
diagnosis is made on the basis of syptoms and blood tests such as blood count, blood
film, renal functions and markers of hemolysis.
– Repeat complete coagulation studies including reaction times
• Prothrombin time (PT), activated partial thromboplastin time (APTT)
• Fibrin degradation products (FDP) – D-dimer
Slightly decreased fibrinogen and slightly prolonged coagulation results.
TTP vs HUS
Often difficult to differentiate
• HUS:
– Microangiopathic hemolytic anemia
– Thrombocytopenia
– Acute renal failure
– Variable CNS symptoms
• NO FEVER!!!!!!!
Cause of MAHA: TTP

The Classic Pentad of TTP
–
–
–
–
–

Microangiopathic hemolytic anemia
Thrombocytopenia
Renal insufficiency or abnormalities
Neurologic abnormalities that can be fluctuating
Fever
√
√
√
√
√
Most common symptoms at presentation are
nonspecific and include abdominal pain, nausea,
vomiting and weakness.
√
Therapy and Prognosis
•
Therapy of MAHA should be initiated immediately due that severe blood loss can
be deadly.
– Transfusion therapy should only be administer to patients with angina or severely
compromised cardiopulmonary status.
– Discontinuing medications and other agents that can cause hemolysis.
– Administer folic acid to avoid pancytopenia.
•
Treatment and Management of TTP
–
–
–
–
•
Plasma exchange, plasma infusion
Splenectomy if plasma exchange fails.
Corticosteroids
NO PLATELET TRANSFUSION!!!
Prognosis:
– Untreated, TTP has a mortality rate of as high as 90%
– With plasma exchange, the mortality rate is reduced to 10-20%.
– Long-term survival is largely dependent on the presence or absence of
serious underlying comorbidities such as cancer, HIV infection, or solid organ
transplantation
Prevention of MAHA
• Prevention of MAHA
will be to get prompt
treatment for the
underlying conditions
causing TTP.
– Inherited and
acquired TTP occur
suddenly with no
clear cause. You
can’t prevent either
type.
http://www.health-writings.com/img/oj/thrombocytopenia-side-effects/blood_clot.jpg
• Mortality reduced to
10-20% with proper tx
• Complete hematologic diagnostic
tests should be performed to link
MAHA to TTP
References
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NEJM 2006; 354:1927-35 George, James MD-Thrombotic Thrombocytopenic Purpura.
Uptodate. Diagnosis, Causes, and Treatment of TTP-HUS
Hematology 2004:407-423.Recent Advances in Thrombotic Thrombocyotopenic Purpura,
Sadler Et al
Hematology 2007. TTP and ADAMTS13: When is testing appropriate? Mannucci et al
Hematology 2006.Thrombocytopenic Purpura:A moving Target. Sadler
Hoffman:Hematology: Basic Principles and Practice fourth edition. Chapters 42 and 132
Swiss Med Wkly 2007;137:518-524. Rituximab for acute plasma refractory thrombotic
thrombocyotopenic purpura.
Eur J Haematology 2005;75:436-440. Acquired TTP as presenting symptom of SLE.
Successful treatment with plasma exchange and immunosuppression-report of 2 cases
Abumuhor, I., & Kearns, H. H. (n.d.). Thrombotic Thrombocytopenic Purpura. In Thrombotic
Thrombocytopenic Purpura (differential diagnosis) [Clinical Cases]. Retrieved August 29,
2006, from School of Health Professions: University of Missouri-Columbia website:
http://www.vhct.org/ case2300/diagnosis.htm
Becker, J. U., MD., & Brenner, B. E., MD., PHD. (2011, April 21). Background. In
Thrombotic Thrombocytopenic Purpur in Emergency Medicine (drugs, conditions, and
procedures) [Reference]. Retrieved May 22, 2011, from WebMD website:
http://emedicine.medscape.com/article/206598-treatment.
Klatt, E. C. (n.d.). Fragmentd Red Blood Cels [Photograph]. Retrieved from
http://library.med.utah.edu/WebPath/HEMEHTML/HEME010.html
Point Spread
Case summary
5
Key Information pointing to Diagnosis
15
Diagnosis
5
Pathophysiology of the disease
25
Diagnostic tests
10
Therapy
5
Prognosis
5
Prevention
5
Take home message
5
Are all questions addressed?
10
Appearance
5
Presentation skills (individual)
5
Total
100