2B von Willebrand disease diagnosis: Considerations reflecting on 2021 multisociety guidelines

The recent American Society of Hematology/ISTH/National Hemophilia Foundation/World Federation of Hemophilia 2021 guidelines on the diagnosis of von Willebrand disease (VWD) is an outstanding effort to unify the diagnosis of VWD. However, as mentioned in the guidelines, there are limitations due to the low certainty in the evidence identified for most questions. The panel encouraged critical review of the guidelines. Compared to other subtypes, there is considerable complexity with diagnosis of type 2B VWD, a type that results from a gain-of-function mutation in the VWF gene. Additionally, the discrimination from its phenocopy platelet-type VWD, representing a gain-of-function mutation in the GP1BA gene, is crucial as this determines treatment decisions. In this forum, we highlight the complexities of a type 2B VWD diagnosis; discuss important issues with respect to these complexities: genotype/phenotype/clinical correlations, challenges with platelet aggregation and ristocetin-induced platelet agglutination testing, platelet count, and thrombocytopathy; and, finally, suggest the consideration of some of these complexities in future iterations of the VWD guidelines.