title: Towards improved diagnosis of von Willebrand disease: comparative evaluations of several automated von Willebrand factor antigen and activity assays.
abstract: BACKGROUND
  von Willebrand disease (VWD) is reportedly the most common bleeding disorder and arises from deficiency and/or defects of von Willebrand factor (VWF). Laboratory diagnosis and typing has important management implications and requires a wide range of tests, including VWF activity and antigen, and involves differential identification of qualitative vs quantitative defects.
  
  
  METHODS
  We have assessed several VWF antigen and activity assays (collagen binding [VWF:CB], ristocetin cofactor [VWF:RCo] and the new Siemens INNOVANCE assay [VWF:Ac], employing latex particles and gain of function recombinant glycoprotein Ib to facilitate VWF binding and agglutination without need for ristocetin) using different instrumentation, including the new Sysmex CS-5100, with a large sample test set (n=600). We included retrospective plus prospective study designs, and also evaluated desmopressin responsiveness plus differential sensitivity to high molecular weight VWF.
  
  
  RESULTS
  VWF:Ag and VWF:RCo results from different methods were respectively largely comparable, although some notable differences were evident, including one high false normal VWF:Ag value (105 U/dL) on a type 3 VWD sample, possibly due to heterophile antibody interference in the latex-based CS-5100 methodology. VWF:Ac was largely comparable to VWF:RCo, but VWF:CB showed discrepant findings to both VWF:RCo and VWF:Ac with some patients, most notably patients with type 2M VWD.
  
  
  CONCLUSIONS
  (a) VWF:Ag on different platforms are largely interchangeable, as are VWF:RCo on different platforms, except for occasional (some potentially important) differences, and manufacturer recommended methods may otherwise require some assay optimization; (b) VWF:RCo and VWF:Ac are largely interchangeable, except for occasional differences that may also relate to assay design (differing optimizations); (c) VWF:CB provides an additional activity to supplement VWF:RCo or VWF:Ac activity assays, and is not interchangeable with either.
authors.affiliation: Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, Westmead Hospital, Westmead, NSW, Australia. Electronic address: emmanuel.favaloro@health.nsw.gov.au.
authors.forename: Emmanuel J
authors.initials: EJ
authors.lastname: Favaloro
authors.affiliation: Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Soma
authors.initials: S
authors.lastname: Mohammed
mesh_terms: D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014842:von Willebrand Diseases / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D014841:von Willebrand Factor / Q000276:immunology*
chemical_list: C029417:Von Willebrand antigen; D014841:von Willebrand Factor
keywords: Collagen binding; INNOVANCE VWF activity; Laboratory testing; Ristocetin cofactor; von Willebrand disease; von Willebrand factor