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

Haemophilia. 2015 Nov;21(6):837-45. doi: 10.1111/hae.12703. Epub 2015 Jul 14.

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.

Keywords: RCo assays; ristocetin; von Willebrand disease; von Willebrand factor.

Publication types

  • Comparative Study

MeSH terms

  • Automation
  • Blood Chemical Analysis / methods*
  • Factor VIII / pharmacology
  • Factor VIII / therapeutic use*
  • Humans
  • Limit of Detection
  • Plasma / chemistry
  • Platelet Aggregation / drug effects
  • Ristocetin / pharmacology
  • Treatment Outcome
  • von Willebrand Diseases / blood
  • von Willebrand Diseases / drug therapy
  • von Willebrand Diseases / physiopathology
  • von Willebrand Factor / metabolism*
  • von Willebrand Factor / pharmacology
  • von Willebrand Factor / therapeutic use*

Substances

  • von Willebrand Factor
  • Ristocetin
  • Factor VIII