Laboratory Testing for von Willebrand Factor Activity by a Glycoprotein Ib-Binding Assay (VWF:GPIbR): HemosIL von Willebrand Factor Ristocetin Cofactor Activity on ACL TOP®

von Willebrand disease (VWD) is a lifelong and common inherited bleeding disorder caused by a quantitative deficiency and/or qualitative defect of von Willebrand factor (VWF). In order to establish the correct diagnosis of VWD, various tests must be conducted, including evaluation of factor VIII activity (FVIII:C), VWF antigen (VWF:Ag), and VWF functional activity. The platelet-dependent VWF activity is measured in different ways, with the historical ristocetin cofactor assay (VWF:RCo) using platelet aggregometry now replaced with newer assays that offer better precision, lower limits of detection, low coefficient of variation, and are fully automated. The VWF activity by glycoprotein Ib-binding assays (VWF:GPIbR) measured on the ACL TOP® platform represents an automated assay that instead of using platelets employs latex beads coated with recombinant wild-type GPIb. VWF in the test sample agglutinates the polystyrene beads coated with GPIb in the presence of ristocetin. The reduction of turbidity as beads agglutinate represents a linear relationship with VWF:GPIbR activity. Using a ratio of VWF:GPIbR/VWF:Ag, the VWF:GPIbR assay also provides good sensitivity and specificity for distinguishing type 1 VWD from type 2. The following chapter describes a detailed protocol for the VWF:GPIbR assay.