Gene Sequencing Aids in Differentiation of von Willebrand Disease Type 2B from Platelet‐Type vWD

Abstract

An elderly female with a positive bleeding history (personal and family) and prior but undocumented diagnosis of von Willebrand disease (vWD) presented for surgery. Testing showed mild thrombocytopenia, decreased ristocetin cofactor activity to von Willebrand factor antigen ratio, and absent high‐molecular‐weight multimers, suggesting a qualitative (type 2) subtype. Low‐dose ristocetin‐induced platelet aggregation demonstrated abnormally increased aggregation, consistent with either type 2B vWD or platelet‐type vWD (PT‐vWD). Differentiation between these subtypes guides therapy. Optimal therapy for type 2B vWD consists of vWF replacement, while platelet transfusions are used to treat PT‐vWD. Traditional options for differentiation include vWF/platelet binding assays or specialized platelet aggregation studies. However, these subspecialized tests have limited availability and sample stability. Gene sequencing performed in our laboratory allowed for detection of 1 of 4 known mutations in GP1BA, (c.763A>;G, p.Met255Val, using standard nomenclature) responsible for PT‐VWD. This finding confirmed her diagnosis and appropriate therapy and facilitates diagnosis for affected family members in this disorder with an autosomal dominant inheritance pattern. Gene sequencing is a useful tool to aid in diagnosis and subtyping of type 2 vWD. kristi.smock@aruplab.com