Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays.

von Willebrand disease (VWD) is considered to be the most common inherited bleeding disorder. VWD is diagnosed following a clinical and physical review, with personal and familial evidence of (primarily mucocutaneous) bleeding, and confirmed by laboratory testing. The latter typically entails initial plasma testing of factor VIII coagulant, von Willebrand factor (VWF) protein ('antigen') and VWF function which has classically been assessed using the ristocetin cofactor (VWF:RCo) assay. More recent attention has focussed on other functional VWF assays, such as collagen binding and so-called 'VWF activity' assays, as possible replacements to the VWF:RCo, or as supplementary tests of VWF 'function'. Additional laboratory testing can comprise a battery of confirmatory and VWD-type assisting assays, including VWF:multimer and von Willebrand factor VIII binding. This review aims to update knowledge of current VWD diagnostics with a particular emphasis on 'functional' VWF assays.