In vitro field study and worldwide survey assessing how clinical haemostasis laboratories analyse recombinant and plasma-derived von Willebrand factor products.

ABSTRACT

INTRODUCTION: Several well-established clinical laboratory methods are available to measure von Willebrand factor (VWF) in plasma samples, but few data are available on their use for analysing recombinant VWF (rVWF). AIM: To evaluate how clinical diagnostic laboratories analyse rVWF and plasma-derived VWF (pdVWF) spiked in vitro into VWF-deficient plasma using quantitative protein and functional assays of VWF. METHODS: Human VWF-deficient plasma samples were spiked with rVWF (vonicog alfa; Takeda) or pdVWF/factor VIII (pdVWF/FVIII; antihemophilic factor/VWF complex [human], CSL Behring), each at final concentrations of 1.0, 0.6, 0.2, 0.1 IU/mL VWFristocetin cofactor activity (VWFRCo) according to labelled VWF activity. The ISTH SSC secondary coagulation standard was used as a control. Participating laboratories received three sets of these blinded aliquots. Mean results per assay were compared with the expected potency based on the labelled VWFRCo activity. RESULTS: Among 39 laboratories, the most commonly established assay was VWFRCo; 22 laboratories reported data from 2214 tests. Despite a trend to lower values, VWFRCo activities for rVWF were in agreement with target concentrations (71%-109%), whereas VWFplatelet glycoprotein Ib (VWFGpIb) and VWF collagen-binding activity (VWFCB) assays gave high recoveries (up to 132% and 127%, respectively). In contrast, pdVWF/FVIII was substantially underestimated by VWFGpIb and VWFCB assays (56%-86% recoveries), whereas the VWFRCo assay gave recoveries of 47%-112% for pdVWF/FVIII. CONCLUSION: The results of VWF assays used in clinical laboratories differ between rVWF and pdVWF, particularly for VWFGpIb and VWFCB assays. These differences may arise from the higher multimeric structure of rVWF compared to pdVWF.