In addition to assessment of
von Willebrand factor (VWF)
antigen (VWF:Ag), the first-line laboratory investigation of possible
von Willebrand disease (VWD) often includes an assay to measure GPIb (
glycoprotein Ib) binding activity of VWF. A decreased GPIb binding activity is characteristic for most of the VWD types. For many years, the most frequently used assay for measuring GPIb binding activity was the
ristocetin cofactor assay (VWF:RCo), which measures the agglutination of fixed human platelets by VWF in the presence of
ristocetin. Because of performance issues, including high assay variability and a lack of VWF sensitivity, this assay is currently being replaced or supplemented by assays based on the binding of VWF to recombinant GPIb. One published method (now abbreviated VWF:GPIbR) uses wild-type GPIb for triggering the binding reaction in the presence of
ristocetin. Another more widely used method (now abbreviated VWF:GPIbM) uses gain-of-function GPIb without
ristocetin; this permits spontaneous binding of VWF to GPIb and avoids problems associated with the nonphysiological substance
ristocetin. The binding of VWF to GPIb can be quantified by using different principles, e.g., ELISA, particle agglutination, or chemiluminescence. The following chapter describes a
ristocetin-free method based on particle agglutination in more detail.