Appropriate laboratory assessment as a critical facet in the proper diagnosis and classification of von Willebrand disorder

Abstract

The correct diagnosis and classification of von Willebrand disease or disorder (VWD) is crucial because the presenting biological activity of von Willebrand factor (VWF) determines both the haemorrhagic risk and the subsequent clinical management. A variety of laboratory assays may be employed, not necessarily restricted to assessments of VWF. Because of assay limitations and von Willebrand disease heterogeneity, no single test procedure is sufficiently ‘robust’ to permit the detection of all VWD variants. Classically, the test panel might include any combination of: (a) skin bleeding time, (b) von Willebrand factor antigen assay, (c) factor VIII C level, (d) assessment of ‘functional’ von Willebrand factor (collagen-binding activity or ristocetin co-factor assay), (e) ristocetin-induced platelet aggregation, and (f) multimer analysis. There have also been many new diagnostic developments that have begun to influence the diagnostic process. These include the automation of existing assay procedures, new automated platelet function analysers such as the PFA-100®, and specific von Willebrand factor–factor VIII-binding assays. This chapter focuses on the recommended laboratory process for the investigation of VWD. The selection of an appropriate combination test panel and testing sequence is crucial for the proper diagnosis and classification of congenital von Willebrand disease.