LABORATORY ASSAYS FOR VON-WILLEBRAND-FACTOR - RELATIVE CONTRIBUTION TO THE DIAGNOSIS OF VON-WILLEBRANDS-DISEASE

Appropriate investigation of a patient with suspected von Willebrand's disease (VWD) involves a clinical assessment of the patient followed by laboratory testing. A variety of laboratory assays may be performed , not necessarily restricted to an assessment of von Willebrand factor (VWF). Due to the limitations of each assay, and because of VWD heter ogeneity, no single test procedure is sufficiently robust to permit de tection of all VWD variants. Indeed, these factors often lead to consi derable confusion in the process of laboratory interpretation regardin g the likelihood of VWD, and the subtype of VWD. This paper attempts t o clarify some of the issues that lead to this confusion. It analyses the relative contribution of four separate assays for VWF [VWF:Multime r analysis, VWF:Antigen (VWF:Ag), VWF:Ristocetin Cofactor (VWF:RCof), and VWF:Collagen Binding Activity assay (VWF:CBA)] to the diagnosis an d classification of VWD. Although each assay detects VWF, it is import ant to recognise that each assay provides different information on the VWF so detected. For example, while the VWF:Ag assay is a quantitativ e assay and provides a very good measure of the overall level or VWF p resent in a patient's plasma, it is not a functional assay and yields no information concerning the quality of the VWF present. Thus, the VW F:AS on its own will not permit detection of many qualitative defects (consequently, use of this assay alone will lead to many Type 2 VWD pa tients being missed by the laboratory). In contrast, the VWF:CBA is a functional assay which provides very useful information on the quality of VWF present. Although the VWF:CBA is also a quantitative assay, it is less sensitive than the VWF:Ag assay in terms of its ability to me asure the overall level of VWF (ie; the VWF:CBA detects only highly ad hesive VWF, and therefore only a proportion of overall VWF). In essenc e, the VWF:Ag and VWF:CBA assays are complementary assays and should b e used in combination. The VWF:Multimer assay is a qualitative procedu re, but at best is only semi-quantitative. The VWF:Multimer assay esse ntially provides a snap-shot of the VWF present. Unfortunately conside rable technical and interpretive problems limits its overall applicabi lity and usefulness. The VWF:RCof assay is both a quantitative and qua litative assay that provides information about the presence of VWF tha t lies between that provided individually by the VWF:Ag and VWF:CBA as says. unfortunately, the VWF:RCof suffers considerable technical probl ems, including considerable assay variability, that also limits its ov erall usefulness. Laboratories performing assays for VWF need to devel op diagnostic strategies which include the use of appropriate multiple test combinations so as to ensure that VWD is properly detected.