title: Discrimination of von Willebrands disease (VWD) subtypes: direct comparison of von Willebrand factor:collagen binding assay (VWF:CBA) with monoclonal antibody (MAB) based VWF-capture systems.
abstract: Discrimination of von Willebrand's Disease (VWD) subtypes is important since it influences management. Qualitative [ie Type 2A, 2B, 2M] defects exhibit von Willebrand factor (VWF) discordance and give high VWF:Ag to VWF:'activity' ratios. Classically, VWF:'activity' is assessed using the VWF:RCof assay. The VWF:CBA is an ELISA-based VWF-functional adhesive assay which has consistently proved to be superior to VWF:RCof. A commercially available monoclonal antibody (MAB) based ELISA assay system claimed to mimic a VWF:RCof-like activity has also been recently described ('SE'), as has the production and characterisation of a large number [n = 10] of locally generated anti-VWF MAB. In the current study, we have adapted these MAB to in-house ELISA assays to assess their utility for VWD diagnosis and subtype discrimination, and to compare them with other assay systems. Thus, the VWF:CBA, VWF:RCof by agglutination, the SE assay, and in-house MAB based assays have been directly compared for their ability to discriminate Type 1 [n = 9] from Type 2 VWD samples [phenotypes 2A and 2B; n = 11]. In summary, MAB-based systems can be used to measure VWF and confirm a diagnosis of VWD, as well as exhibiting some VWD-subtype-discriminatory capabilities. However, better evidence of VWF-discordance was usually achieved using the VWF:RCof (agglutination) assay, while the greatest degree of VWF-discordance was consistently observed using the VWF:CBA assay. In conclusion, the VWF:CBA assay proved to offer the best diagnostic predictive tool for a Type 2 VWD defect, while MAB-based systems appear to be less effective in this regard.
authors.affiliation: Department of Haematology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, NSW, Australia. emmanuel@icpmr.wsahs.nsw.gov.au
authors.forename: E J
authors.initials: EJ
authors.lastname: Favaloro
authors.forename: A
authors.initials: A
authors.lastname: Henniker
authors.forename: D
authors.initials: D
authors.lastname: Facey
authors.forename: M
authors.initials: M
authors.lastname: Hertzberg
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001681:Biological Assay; D003094:Collagen; D006801:Humans; D011485:Protein Binding; D014842:von Willebrand Diseases / Q000145:classification / Q000175:diagnosis*; D014841:von Willebrand Factor / Q000032:analysis* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014841:von Willebrand Factor; D003094:Collagen