A 6-year-old boy with a lifelong history of mucosal bleeding has a platelet count of 90,000 per microliter. Ristocetin-induced platelet agglutination is enhanced at low concentrations of ristocetin. His father received desmopressin for the same disorder and developed worsening thrombocytopenia. The defect lies in:

• A Autoantibody against the GP Ib-IX-V complex
• B Quantitative deficiency of von Willebrand factor
• C Defect in the alpha-granule release pathway
• D Qualitative gain-of-function mutation in the platelet binding domain (A1 domain) of von Willebrand factor ✓

Explanation

Type 2B von Willebrand disease results from a qualitative gain-of-function mutation in the D1 domain, increasing affinity of vWF for platelet GP Ib. Spontaneous binding clears both platelets and large vWF multimers, giving thrombocytopenia and enhanced low-dose ristocetin agglutination. Desmopressin releases abnormal multimers and can precipitate platelet aggregation, so it is contraindicated. Type 1 is quantitative deficiency with reduced ristocetin response, and Bernard-Soulier shows absent ristocetin agglutination.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.