Activation, activity and inactivation of factor VIII in factor VIII products

Haemophilia : the Official Journal of the World Federation of Hemophilia
Thomas OrfeoS Butenas

Abstract

Factor VIII (FVIII) products used in haemophilia A treatment show inter-and intra-product and inter-assay differences in specific activity. The mechanistic basis of these differences remains unclear. The aim of this study was to mechanistically compare the functional properties of an in-house excipient-free full-length FVIII standard and pharmacologic recombinant products containing full-length (products A and B) or B-domainless (C and D) FVIII. Factor VIII protein concentration was quantitated by ELISA. Product potency determinations (APTT, intrinsic tenase assays) and kinetic analyses detailing these products' activations by thrombin and FXa, their spontaneous and activated protein C (APC) catalysed inactivation and their performances in coagulation proteome reconstructions were studied +/- von Willebrand factor (VWF). Computational models were developed to facilitate interpretation of empirical data. Factor VIII protein content per manufacturer activity unit was highest for product C with the other three products similar to the standard. Potency estimates, done five different ways, varied 20-30% in inter- and intra-assay comparisons, with product B consistently showing lower specific activity. Kinetic analyses showed the fiv...Continue Reading

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Citations

Oct 28, 2016·Journal of Thrombosis and Haemostasis : JTH·M GisselT Orfeo

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