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Difficulty: MediumHematology and Oncology

Brought to the emergency department by his wife, a 41-year-old man has exhibited worsening fatigue, severe headache, and episodic confusion over the past four days. His wife mentions that his behavior has been highly uncharacteristic. His past medical history includes major depressive disorder, for which he was recently prescribed fluoxetine. His temperature is 38.1°C (100.6°F), blood pressure is 145/88 mm Hg, and pulse is 102/min. Physical examination reveals scattered petechiae over his bilateral lower extremities and mild scleral icterus. Neurologic examination shows no focal deficits, but the patient is disoriented to time and place. Cardiopulmonary examination is unremarkable.

Laboratory studies show:
Hemoglobin: 7.8 g/dL
Platelet count: 18,000/µL
Leukocyte count: 8,400/µL
Creatinine: 2.1 mg/dL
Total bilirubin: 3.8 mg/dL
Indirect bilirubin: 3.2 mg/dL
Lactate dehydrogenase: 1,100 U/L

A peripheral blood smear demonstrates numerous fragmented red blood cells. Which of the following is the most appropriate next step in management for this patient?

  1. Plasma exchangeAnswer
  2. B
    Intravenous platelet transfusion
  3. C
    Discontinuation of fluoxetine and administration of cyproheptadine
  4. D
    Intravenous broad-spectrum antibiotics and lumbar puncture
  5. E
    Intravenous corticosteroids and intravenous immunoglobulin

Answer

Plasma exchange
The correct answer is plasma exchange. This patient presents with the classic pentad of thrombotic thrombocytopenic purpura (TTP): microangiopathic hemolytic anemia (MAHA), thrombocytopenia, acute kidney injury, neurologic abnormalities, and fever. The peripheral blood smear showing numerous fragmented red blood cells (schistocytes) combined with elevated LDH and indirect hyperbilirubinemia confirms MAHA. TTP is a hematologic emergency caused by decreased activity of the von Willebrand factor-cleaving protease ADAMTS13, usually due to an acquired autoantibody. This leads to the formation of abnormally large vWF multimers that consume platelets and cause widespread microvascular thrombosis. Immediate plasma exchange is the life-saving treatment of choice, as it removes the circulating autoantibodies and replenishes the ADAMTS13 enzyme. Glucocorticoids are often administered concurrently.

Step-by-Step Solution

1
Analyze the clinical presentation and laboratory findings.
The patient has the classic pentad of fever, neurologic symptoms (confusion), renal failure (elevated creatinine), thrombocytopenia, and microangiopathic hemolytic anemia (MAHA) indicated by anemia, elevated indirect bilirubin, high LDH, and schistocytes.
Identifying these five features confirms the clinical diagnosis of thrombotic thrombocytopenic purpura (TTP).
2
Determine the pathophysiology of the suspected diagnosis.
TTP is caused by a severe deficiency of ADAMTS13, a von Willebrand factor (vWF)-cleaving protease, leading to large vWF multimers that cause platelet aggregation and microvascular thrombosis.
Understanding the underlying mechanism is essential to select the appropriate targeted therapy.
3
Identify the most appropriate next step in management.
Plasma exchange (plasmapheresis) is the primary treatment. It removes the autoantibodies against ADAMTS13 and replenishes the missing enzyme.
Without prompt plasma exchange, the mortality rate for TTP exceeds 90%.

Key Concept

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening hematologic emergency characterized by microangiopathic hemolytic anemia and thrombocytopenia. Immediate treatment with plasma exchange is required.
Estimated Time:1m 30s
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Topics

Hematology and Oncology

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