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Difficulty: HardHematology and Oncology

Emergency medical responders bring a 42-year-old female teacher to the emergency department after she was found profoundly disoriented in her classroom. Her husband reports she has experienced worsening fatigue, diffuse headaches, and nausea over the past three days. She has no significant past medical history and takes no medications. On arrival, her temperature is 38.2°C (100.8°F), blood pressure is 145/90 mmHg, pulse is 112/min, and respirations are 18/min. Physical examination is notable for lethargy, mild scleral icterus, and widespread nonblanching purple pinpoint spots over her lower extremities.

Laboratory studies reveal the following:

ParameterResultReference Range
Hemoglobin7.8 g/dL12.0-16.0 g/dL
Platelets18,000/mm³150,000-400,000/mm³
Leukocytes9,500/mm³4,500-11,000/mm³
Blood urea nitrogen34 mg/dL7-18 mg/dL
Creatinine1.9 mg/dL0.6-1.2 mg/dL
Total bilirubin3.8 mg/dL0.1-1.2 mg/dL
Indirect bilirubin2.9 mg/dL0.1-0.8 mg/dL
Lactate dehydrogenase1,250 U/L100-250 U/L
Prothrombin time12 sec11-15 sec
Activated PTT28 sec25-40 sec
Fibrinogen350 mg/dL150-400 mg/dL

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

  1. Initiation of plasma exchangeAnswer
  2. B
    Transfusion of pooled platelet concentrates
  3. C
    Transfusion of fresh frozen plasma and cryoprecipitate
  4. D
    Deferral of specific therapy pending ADAMTS13 activity results
  5. E
    Administration of broad-spectrum intravenous antibiotics and lumbar puncture

Answer

The most appropriate next step in management is the initiation of plasma exchange.
The correct action is the initiation of plasma exchange. This patient presents with the classic pentad of Thrombotic Thrombocytopenic Purpura (TTP): fever, altered mental status, thrombocytopenia, acute kidney injury (elevated BUN/Creatinine), and microangiopathic hemolytic anemia (anemia, elevated indirect bilirubin, highly elevated LDH, and schistocytes). TTP is caused by severely decreased activity of the von Willebrand factor (vWF)-cleaving protease ADAMTS13, usually due to an acquired autoantibody. This leads to the formation of ultra-large vWF multimers that shear red blood cells and consume platelets in microthrombi throughout the body. Because it is rapidly fatal without treatment, plasma exchange must be initiated immediately upon clinical suspicion. Plasma exchange removes the autoantibodies and the ultra-large vWF multimers, while concurrently replacing the deficient ADAMTS13 enzyme.

Step-by-Step Solution

1
Analyze the clinical presentation and laboratory results to form a diagnosis.
The patient exhibits the classic pentad of Thrombotic Thrombocytopenic Purpura (TTP): microangiopathic hemolytic anemia (MAHA), severe thrombocytopenia, fever, acute kidney injury, and altered mental status.
Recognizing the constellation of symptoms is essential for identifying microangiopathic disorders.
2
Differentiate the suspected diagnosis from other similar coagulopathies.
The normal prothrombin time (PT), normal activated partial thromboplastin time (aPTT), and normal fibrinogen levels rule out Disseminated Intravascular Coagulation (DIC).
DIC involves the massive consumption of coagulation factors, prolonging PT/aPTT, whereas TTP is primarily an issue of platelet aggregation leaving the coagulation cascade intact.
3
Determine the optimal immediate therapeutic intervention.
Plasma exchange (plasmapheresis) must be initiated immediately without waiting for confirmatory ADAMTS13 laboratory results.
TTP is a medical emergency with a high mortality rate if untreated. Plasma exchange rapidly removes the offending autoantibodies and ultra-large von Willebrand factor multimers while replacing the deficient ADAMTS13 enzyme.

Key Concept

Diagnosis and emergent management of Thrombotic Thrombocytopenic Purpura (TTP)
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Topics

Hematology and Oncology

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