Characterisation of the p.A1461D mutation causing von Willebrand disease type 2B with severe thrombocytopenia, circulating giant platelets, and defective alpha-granule secretion

摘要

Von Willebrand disease type 2B (VWD2B) is a rare bleeding disorder affecting 5-8% of all VWD patients. The disorder is characterised by enhanced binding of von Willebrand factor (VWF) to platelet glycopro-tein Ib alpha (GPIba) due to gain-of-func-tion mutations clustering in the VWF Al domain (1), which may result in spontaneous platelet agglutination and increased ADAMTS13-mediated VWF proteolysis (2, 3). Consequently, thrombocytopenia, loss of larger VWF plasma multimers, and increased agonist-induced platelet agglutination at low concentrations of ristocetin (i.e. <0.8 mg/ml) are typical findings in VWD2B (4). However, not all of these features must be present, and confirming a diagnosis of VWD2B can thus be challenging-