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Difficulty: HardHematology and Oncology

A 42-year-old woman is brought to the emergency department by her husband due to progressive confusion and lethargy over the past 2 days. She has also reported generalized weakness and dark urine. Her temperature is 38.1°C (100.6°F), blood pressure is 142/88 mmHg, pulse is 112/min, and respirations are 18/min. Physical examination reveals scleral icterus and scattered petechiae over her bilateral lower extremities. Neurologic examination shows a lethargic patient who is oriented to person only, with no focal motor or sensory deficits. Laboratory studies show the following:

Laboratory TestResultReference Range
Hemoglobin7.8 g/dL12.0-15.5 g/dL
Platelets24,000/mm³150,000-400,000/mm³
Leukocytes8,400/mm³4,500-11,000/mm³
Blood urea nitrogen35 mg/dL7-18 mg/dL
Serum creatinine1.9 mg/dL0.6-1.2 mg/dL
Total bilirubin3.8 mg/dL0.1-1.0 mg/dL
Indirect bilirubin3.2 mg/dL0.1-0.8 mg/dL
Lactate dehydrogenase1,450 U/L100-250 U/L
Prothrombin time12 sec11-15 sec
Partial thromboplastin time30 sec25-40 sec

A peripheral blood smear demonstrates numerous fragmented red blood cells (schistocytes). Which of the following is the most appropriate next step in management?

  1. A
    Platelet transfusion
  2. B
    Intravenous heparin
  3. Plasma exchange therapyAnswer
  4. D
    Intravenous ceftriaxone and vancomycin
  5. E
    Intravenous methylprednisolone monotherapy

Answer

Plasma exchange therapy
The correct answer identifies plasma exchange as the most appropriate initial therapy. This patient is presenting with classic signs of Thrombotic Thrombocytopenic Purpura (TTP): thrombocytopenia, microangiopathic hemolytic anemia (MAHA, evidenced by anemia, high LDH, elevated indirect bilirubin, and schistocytes), acute kidney injury, fever, and neurologic abnormalities. This 'pentad' is driven by a deficiency of the ADAMTS13 enzyme, often due to an acquired autoantibody. Without ADAMTS13, ultra-large von Willebrand factor multimers accumulate and shear passing red blood cells while consuming platelets in microthrombi. Plasma exchange (plasmapheresis) is the gold standard and lifesaving treatment because it removes the offending autoantibodies and replenishes the functional ADAMTS13 enzyme.

Step-by-Step Solution

1
Analyze the clinical presentation and physical exam.
The patient has fever, neurologic symptoms (confusion, lethargy), and petechiae.
Identifying the classic symptoms helps form a differential diagnosis for systemic illness with hematologic manifestations.
2
Evaluate the laboratory results and peripheral smear.
Severe thrombocytopenia, microangiopathic hemolytic anemia (high LDH, indirect hyperbilirubinemia, schistocytes), acute kidney injury, and normal PT/PTT.
These lab findings confirm a thrombotic microangiopathy and effectively rule out Disseminated Intravascular Coagulation (DIC), which would present with elevated PT/PTT.
3
Synthesize findings to make a diagnosis.
The clinical pentad of fever, neurologic changes, renal failure, thrombocytopenia, and microangiopathic hemolytic anemia points to Thrombotic Thrombocytopenic Purpura (TTP).
TTP is caused by a severe deficiency of ADAMTS13, a von Willebrand factor-cleaving protease, leading to large vWF multimers that trap platelets and shear red blood cells.
4
Determine the next most appropriate step in management.
Immediate plasma exchange (plasmapheresis) is required.
Plasma exchange removes the circulating autoantibodies against ADAMTS13 and provides functional ADAMTS13 enzyme from donor plasma, rapidly reversing the microthrombi formation.

Key Concept

Diagnosis and acute management of Thrombotic Thrombocytopenic Purpura (TTP).
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Topics

Hematology and Oncology

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