Impact of different inhibitor reactivities with commercial factor VIII concentrates on thrombin generation

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Abstract
Summary. In order to describe the haemostatic role of a variation in inhibitor reactivity with different factor VIII (FVIII) concentrates, we have compared inhibitor titres against a panel of FVIII concentrates and correlated titre with the capacity to inhibit thrombin generation. Three plasma‐derived concentrates were tested in vitro in mixing experiments with inhibitor plasmas from 11 patients with severe haemophilia A: Fanhdi, which contains von Willebrand factor (VWF) with a final ratio of approximately 1:1 (VWF IU per IU FVIII:C); Haemate‐P with a ratio of 2.5:1 and Hemofil‐M containing only trace amounts of VWF. In addition, the recombinant FVIII concentrate Kogenate Bayer containing no VWF was included. Inhibitor titres and the capacity to generate thrombin were measured. A statistically significant difference in measured titres was found with the highest titres recorded against Hemofil‐M. The inhibitor titres needed to inhibit 50% maximum thrombin generation were the lowest for Kogenate Bayer and the highest and similar for Fanhdi and Haemate‐P with intermediate titres needed for inhibition of Hemofil‐M. In this study, the thrombin generation assay provides additional indications for the role of VWF in the treatment of patients with inhibitors. The VWF‐containing concentrates Fanhdi and Haemate‐P, added to FVIII‐deficient plasma with the presence of inhibitor, generate more thrombin than do the purified concentrates Hemofil‐M and Kogenate Bayer.