A patient with thrombotic thrombocytopenic purpura (TTP) has ADAMTS13 activity <10% of normal. ADAMTS13 normally cleaves which substrate?

• A Fibrin cross-links formed by factor XIIIa
• B Unusually large von Willebrand factor multimers at the Tyr1605-Met1606 bond ✓
• C Platelet glycoprotein Ib (GPIb) preventing its interaction with von Willebrand factor
• D C3b deposited on endothelial surfaces (complement regulation)

Explanation

ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) cleaves ultra-large von Willebrand factor multimers at the Tyr1605-Met1606 bond within the VWF A2 domain, under conditions of shear stress. Without ADAMTS13 (absent in acquired TTP due to autoantibodies, or in hereditary TTP/Upshaw-Schulman syndrome), ultra-large VWF multimers accumulate on endothelium and in plasma, promoting platelet adhesion and aggregation, causing microvascular thrombi (thrombocytopenia, MAHA, organ ischemia). Factor XIIIa is inhibited by different mechanism.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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