title: Use of the collagen-binding assay for von Willebrand factor in the analysis of type 2M von Willebrand disease: a comparison with the ristocetin cofactor assay.
abstract: This study compares the utility of two functional assays for von Willebrand factor (VWF), the ristocetin cofactor assay (VWF:RCo) and the collagen-binding assay (VWF:CBA). We analysed a group of 32 patients with type 2 von Willebrand disease (VWD) (25 patients with type 2M, six with type 2A and one with type 2B) and 22 normal control subjects. VWF:RCo/VWF antigen (VWF:Ag) ratios and VWF:CBA/VWF:Ag ratios were compared between the patient and control groups. In the six patients with type 2A VWD, both VWF:RCo/VWF:Ag ratios and VWF:CBA/VWF:Ag ratios were discordant (< or = 0.7). In the 25 type 2M VWD patients, the VWF:CBA/VWF:Ag ratios were concordant (> 0.7), but the VWF:RCo/VWF:CBA ratios were discordant (< or = 0.7) (P = 0.001) compared with control subjects. Thus, VWF:RCo/VWF:Ag ratios were discordant in both type 2M and 2A VWD patient groups indicating a functional abnormality. However, VWF:CBA/VWF:Ag ratios were discordant in the type 2A VWD group but not in the type 2M VWD group. Our study showed that VWF:CBA is sensitive to functional variants associated with the loss of high-molecular-weight multimers, i.e. type 2A and 2B in VWD, but the assay was unable to discriminate defective platelet-binding VWD variants with normal multimeric patterns such as type 2M VWD. It was concluded that the VWF:CBA assay should be used in association with rather than as a replacement for the VWF:RCo assay.
authors.affiliation: Katharine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Riddell
authors.forename: P Vincent
authors.initials: PV
authors.lastname: Jenkins
authors.forename: Ioana C
authors.initials: IC
authors.lastname: Nitu-Whalley
authors.forename: Angus H
authors.initials: AH
authors.lastname: McCraw
authors.forename: Christine A
authors.initials: CA
authors.lastname: Lee
authors.forename: Simon A
authors.initials: SA
authors.lastname: Brown
mesh_terms: D016022:Case-Control Studies; D024061:Collagen Type III / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010974:Platelet Aggregation; D011237:Predictive Value of Tests; D011485:Protein Binding; D012310:Ristocetin; D018709:Statistics, Nonparametric; D014842:von Willebrand Diseases / Q000145:classification* / Q000276:immunology; D014841:von Willebrand Factor / Q000032:analysis* / Q000276:immunology
chemical_list: D024061:Collagen Type III; D014841:von Willebrand Factor; D012310:Ristocetin