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Transfusion Thresholds-Cardiovascular Disease — MRCP Part 1 MCQ

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HardHematologyTransfusion Thresholds-Cardiovascular DiseaseMRCP Part 1

A patient treated for acute immune TTP has melena while receiving caplacizumab. Which molecular interaction is inhibited by this drug and explains both efficacy and bleeding risk?

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Correct answer: D — Platelet glycoprotein-Ib binding to the VWF A1 domain

The best answer is “Platelet glycoprotein-Ib binding to the VWF A1 domain”. Caplacizumab is a bivalent nanobody directed against the von Willebrand factor A1 domain. It prevents A1 engagement with platelet glycoprotein Ib, rapidly limiting platelet-rich microthrombi but increasing mucocutaneous bleeding. It does not restore ADAMTS13, inhibit complement C5, block integrin alpha-IIb-beta-3 or target P-selectin. That mechanism explains why immunosuppression and plasma exchange remain necessary alongside caplacizumab.

Reference: ISTH guideline for treatment of thrombotic thrombocytopenic purpura: https://pmc.ncbi.nlm.nih.gov/articles/PMC8091490/