Case StudyMICR 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

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%

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

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.

Microangiopathic Hemolytic Anemia (MAHA)

*Intravascular Hemolysis is also associated with the presence of Schistocytes

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: TTPCause of MAHA: TTP

The Classic Pentad of TTPThe Classic Pentad of TTP– Microangiopathic hemolytic anemia Microangiopathic hemolytic anemia √√– Thrombocytopenia Thrombocytopenia √√– Renal insufficiency or abnormalitiesRenal insufficiency or abnormalities √√– Neurologic abnormalities that can be fluctuating √Neurologic abnormalities that can be fluctuating √– FeverFever √√

Most common symptoms at presentation are Most common symptoms at presentation are nonspecific and include abdominal pain, nausea, nonspecific and include abdominal pain, nausea, vomiting and weakness.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

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 SpreadCase 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