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  • Title: Laboratory assays for von Willebrand factor: relative contribution to the diagnosis of von Willebrand's disease.
    Author: Favaloro EJ, Koutts J.
    Journal: Pathology; 1997 Nov; 29(4):385-91. PubMed ID: 9423220.
    Abstract:
    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 heterogeneity, no single test procedure is sufficiently robust to permit detection of all VWD variants. Indeed, these factors often lead to considerable confusion in the process of laboratory interpretation regarding the likelihood of VWD, and the subtype of VWD. This paper attempts to clarify some of the issues that lead to this confusion. It analyses the relative contribution of four separate assays for VWF [VWF:Multimer analysis, VWF:Antigen (VWF:Ag), VWF:Ristocetin Cofactor (VWF:RCof), and VWF:Collagen Binding Activity assay (VWF:CBA)] to the diagnosis and classification of VWD. Although each assay detects VWF, it is important to recognise that each assay provides different information on the VWF so detected. For example, while the VWF:Ag assay is a quantitative assay and provides a very good measure of the overall level of VWF present in a patient's plasma, it is not a functional assay and yields no information concerning the quality of the VWF present. Thus, the VWF:Ag on its own will not permit detection of many qualitative defects (consequently, use of this assay alone will lead to many Type 2 VWD patients 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 measure the overall level of VWF (i.e.; the VWF:CBA detects only highly adhesive VWF, and therefore only a proportion of overall VWF). In essence, the VWF:Ag and VWF:CBA assays are complementary assays and should be used in combination. The VWF:Multimer assay is a qualitative procedure, but at best is only semi-quantitative. The VWF:Multimer assay essentially provides a snap-shot of the VWF present. Unfortunately considerable technical and interpretive problems limits its overall applicability and usefulness. The VWF:RCof assay is both a quantitative and qualitative assay that provides information about the presence of VWF that lies between that provided individually by the VWF:Ag and VWF:CBA assays. Unfortunately, the VWF:RCof suffers considerable technical problems, including considerable assay variability, that also limits its overall usefulness. Laboratories performing assays for VWF need to develop diagnostic strategies which include the use of appropriate multiple test combinations so as to ensure that VWD is properly detected.
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