Classification of von Willebrand disease in the context of modern contemporary von Willebrand factor testing methodologies

von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder, potentially affecting up to 1% of the population according to epidemiologic data, although numbers based on presentation to clinics are closer to 0.1%.¹ VWD arises from defects and/or deficiency of von Willebrand factor (VWF), and laboratory testing assists clinical exclusion or diagnosis.^2-5 Contemporary laboratory assays comprise VWF antigen (VWF:Ag), markers of VWF activity, and factor VIII activity (FVIII:C),^2-7 using various methods. There are many VWF activity assays, especially those reflective of glycoprotein Ib (GPIb) binding (including classical ristocetin cofactor [VWF:RCo]), and for which the VWF/VWD Scientific Standardisation Committee (SSC) of the ISTH has recommended revised nomenclature.^{5, 7} VWF:RCo assays using platelets, ristocetin, and native GPIb remain VWF:RCo, but those using other solid-phase particles and recombinant GPIb are termed VWF:GPIbR.^{5, 7} Additional gain-of-function VWF assays using recombinant GPIb mutations reflect VWF:GPIb binding assays similar to VWF:RCo and VWF:GPIbR but that do not employ ristocetin are termed VWF:GPIbM.^{5, 7-9} Another distinct category of VWF activity assay is the collagen binding assay (VWF:CB).^{5, 10} Assessment of VWF multimers by gel electrophoresis also has a place in VWD diagnosis, although classical methods are nonstandardized, complex, time consuming, and subject to high error rates in diagnostic practice.^{11, 12}