Von Willebrand factor collagen binding activity in the diagnosis of von Willebrand disease: an alternative to ristocetin co-factor activity?

The capability of von Willebrand factor (VWF) to bind platelet glycoprotein Ib (GPIb) and promote platelet plug formation is currently evaluated in vi tro using the ristocetin co-factor activity (VWF:RCo) assay The replacement of this cumbersome and not always reproducible test with the collagen bind ing activity of VWF (VWF:CBA) has been attempted with controversial results . To evaluate the capacity of VWF:CBA to identify classic and variant von W illebrand disease (VWD) compared with VWF:RCo, we studied 10 type 2A and 12 type 2B VWD patients, together with 30 type 1 VWD patients with reduced pl atelet VWF content. In both 24 and 2B VWD, VWF:CBA and VWF:RCo were decreas ed, but that of VWF:CBA was more consistent, The difference was more eviden t when values were expressed as a ratio, obtained by normalizing VWF:CBA an d VWF:RCo with the VWF antigen value; the ratio for VWF:CBA was always belo w 0.2, while that for VWF:RCo was greater than 0.4. and in no patient was t he VWF:CBA value higher than VWF:RCo. In contrast, in type 1 VWD, the decre ase in VWF:CBA. was similar to that seen in VWF:RCo with the ratios always within the normal range. To better investigate the relationship between VWF :CBA and VWF:RCo, and the representation of large/intermediate VWF multimer s, to which both tests are sensitive, deamino-cys-8-D-arginine-vasopressin (DDAVP) was infused in type 2A and 2B VWD patients. The differences between the two tests were even more evident after DDAVP, and in type ZA, even tho ugh large multimers were persistently decreased, VWF:RCo was normalized, wh ile VWF:CBA remained defective. These findings clearly indicate that VWF:CB A detects the absence of large and intermediate VWF multimers better than V WF:RCo. Hence, we suggest adding VWF:CBA to the panel of tests employed in the diagnosis of VWD. Moreover, owing to the difficulty in performing VWF:R Co and its low reproducibility, we suggest that, when necessary, VWF:CBA ma y be substituted for VWF:RCo.