A patient with thrombotic thrombocytopenic purpura (TTP) shows the classic pentad of features. The underlying pathogenesis involves deficiency or inhibition of which enzyme?

• A Protein C — a natural anticoagulant cleaving activated factors Va and VIIIa
• B Plasminogen activator — responsible for fibrinolysis
• C ADAMTS13 — a von Willebrand factor-cleaving metalloprotease ✓
• D Factor H — a complement regulatory protein

Explanation

TTP results from deficiency or autoantibody-mediated inhibition of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), the enzyme that cleaves ultra-large VWF multimers. Without ADAMTS13, ultra-large VWF multimers accumulate, causing spontaneous platelet aggregation in microvessels, platelet consumption (thrombocytopenia), and microangiopathic hemolytic anemia. Factor H deficiency causes atypical HUS (complement-mediated TMA). Protein C deficiency causes thrombosis without TMA. Plasminogen activator deficiency impairs fibrinolysis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.