title: Comparison of several von Willebrand factor (VWF) activity assays for monitoring patients undergoing treatment with VWF/FVIII concentrates: improved performance with a new modified automated method.
abstract: BACKGROUND
  The ability of von Willebrand factor (VWF) to bind platelet GP Ib and promote platelet plug formation is measured in vitro using the ristocetin cofactor (VWF:RCo) assay. Automated assay systems make testing more accessible for diagnosis, but do not necessarily improve sensitivity and accuracy.
  
  
  OBJECTIVE
  We assessed the performance of a modified automated VWF:RCo assay protocol for the Behring Coagulation System (BCS(®) ) compared to other available assay methods.
  
  
  METHODS
  Results from different VWF:RCo assays in a number of specialized commercial and research testing laboratories were compared using plasma samples with varying VWF:RCo activities (0-1.2 IU mL(-1) ). Samples were prepared by mixing VWF concentrate or plasma standard into VWF-depleted plasma. Commercially available lyophilized standard human plasma was also studied. Emphasis was put on the low measuring range. VWF:RCo accuracy was calculated based on the expected values, whereas precision was obtained from repeated measurements.
  
  
  RESULTS
  In the physiological concentration range, most of the automated tests resulted in acceptable accuracy, with varying reproducibility dependent on the method. However, several assays were inaccurate in the low measuring range. Only the modified BCS protocol showed acceptable accuracy over the entire measuring range with improved reproducibility.
  
  
  CONCLUSIONS
  A modified BCS(®) VWF:RCo method can improve sensitivity and thus enhances the measuring range. Furthermore, the modified BCS(®) assay displayed good precision. This study indicates that the specific modifications - namely the combination of increased ristocetin concentration, reduced platelet content, VWF-depleted plasma as on-board diluent and a two-curve calculation mode - reduces the issues seen with current VWF:RCo activity assays.
authors.affiliation: Malmö Centre for Thrombosis and Haemostasis, Department of Clinical Chemistry, Malmö University Hospital, Malmö, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Hillarp
authors.affiliation: Medical Sciences Institute, Blood Center of Wisconsin and Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Friedman
authors.affiliation: Colorado Coagulation, Laboratory Corporation of America® Holdings, Englewood, CO, USA.
authors.forename: D
authors.initials: D
authors.lastname: Adcock-Funk
authors.affiliation: Colorado Coagulation, Laboratory Corporation of America® Holdings, Englewood, CO, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tiefenbacher
authors.affiliation: Special Coagulation Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: Nichols
authors.affiliation: Special Coagulation Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.affiliation: Octapharma OPG, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Stadler
authors.affiliation: Octapharma USA, Hoboken, NJ, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Schwartz
mesh_terms: D001331:Automation; D001774:Blood Chemical Analysis / Q000379:methods*; D005169:Factor VIII / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D057230:Limit of Detection; D010949:Plasma / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects; D012310:Ristocetin / Q000494:pharmacology; D016896:Treatment Outcome; D014842:von Willebrand Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D014841:von Willebrand Factor / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014841:von Willebrand Factor; D012310:Ristocetin; D005169:Factor VIII
keywords: RCo assays; ristocetin; von Willebrand disease; von Willebrand factor