1. Case Study MICR 410 - Hematology Spring, 2011
Jazmin Graff
Barbara Huang
Marian Navarrete

2. 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.

3. Key Information Pointing to Diagnosis
Table 1: Laboratory Results
Test
Result
Normal Range
Hemoglobin
6.0 g/dL
g/dL
Hematocrit
0.18 L/L
L/L
White Blood Cells
8.9 x 109/L
x109/L
Platelet
31 x109/L
x109/L
Reticulocyte
2.5%
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 2: Results of urinalysis
Protein 2+
Blood +
* Renal insufficiencies

4. 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)

5. 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.

6. 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.

7. Microangiopathic Hemolytic Anemia (MAHA)
Morphology : Fragmented Cells
Possible Pathology
Burr Cells
Renal Disease
Liver Disease
Burns
Schistocyte
Prosthetic Heart Valve
Microangiopathic Hemolytic Anemia
Disseminated Intravascular Coagulation
Thrombotic Thrombocytopenic Purpura
Hemolytic Uremic Syndrome
Clostridial Infections
Helmet Cells
G6PD Deficiency
Pulmonary Emboli
*Intravascular Hemolysis is also associated with the presence of Schistocytes
Microangiopathic Hemolytic Anemia (MAHA)

8. 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
Coagulation tests to rule of ITP and DIC!!!!

9. ITP: Idiopathic thrombocytopenic purpura
TTP: thrombotic thrombocytopenic purpura
DIC: Disseminated Intravascular Coagulation
Slightly decreased fibrinogen and slightly prolonged coagulation results.

10. TTP vs HUS Often difficult to differentiate HUS:
– Microangiopathic hemolytic anemia
– Thrombocytopenia
– Acute renal failure
– Variable CNS symptoms
NO FEVER!!!!!!!

11. 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. √

12. 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
MI and stroke if give platelets!!!

13. 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.

14. (anemia caused by intravascular destruction of cells)
Diagnosis: MAHA
(anemia caused by intravascular destruction of cells)
Complete hematologic diagnostic
tests should be performed to link
MAHA to TTP
Mortality reduced to
10-20% with proper tx

15. References
NEJM 2006; 354: George, James MD-Thrombotic Thrombocytopenic Purpura.
Uptodate. Diagnosis, Causes, and Treatment of TTP-HUS
Hematology 2004: Recent Advances in Thrombotic Thrombocyotopenic Purpura, Sadler Et al
Hematology 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: Rituximab for acute plasma refractory thrombotic thrombocyotopenic purpura.
Eur J Haematology 2005;75: 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: 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:
Klatt, E. C. (n.d.). Fragmentd Red Blood Cels [Photograph]. Retrieved from

16. Point Spread Case summary 5 Key Information pointing to Diagnosis 15
Pathophysiology of the disease 25
Diagnostic tests 10
Therapy
Prognosis
Prevention
Take home message
Are all questions addressed?
Appearance
Presentation skills (individual)
Total
100