A patient with TTP (thrombotic thrombocytopenic purpura) has a severe deficiency of ADAMTS13. Which mechanism directly causes thrombocytopenia and microangiopathic hemolytic anemia?
- A Persistence of ultra-large von Willebrand factor multimers causing platelet aggregation in microvasculature ✓
- B Antibody-mediated platelet destruction in the spleen
- C Deposition of fibrin in microvasculature from uncontrolled thrombin generation
- D Complement-mediated platelet lysis via MAC formation
Correct answer: A. Persistence of ultra-large von Willebrand factor multimers causing platelet aggregation in microvasculature
Explanation
ADAMTS13 is the metalloprotease that cleaves ultra-large von Willebrand factor (ULVWF) multimers secreted by endothelium. In TTP, severe ADAMTS13 deficiency (usually immune-mediated) allows ULVWF to accumulate, spontaneously bind platelet GPIb, and form microthrombi in small vessels. Platelet consumption causes thrombocytopenia; RBCs are mechanically sheared by platelet-fibrin microthrombi causing MAHA. In HUS, Shiga toxin damages endothelium with fibrin deposition.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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