Fibrinopeptide A release by factor-IX concentrates and FEIBA fraction (factor eight inhibitor bypassing activity).

Abstract

Abstract Factor IX-concentrates (FC) can cause in vivo activation of the coagulation system. To detect either thrombin presence or generation in vitro, the release of fibrinopeptide A (FPA) from fibrinogen added to FC or activated FEIBA fractions has been measured by a specific radioimmunoassay. In none of 8 batches thrombin was detected. However, the addition of CaCl 2 led to thrombin generation, which was high in 3 and moderate in 5 concentrates. Prior addition of heparin could fully inhibit the CaCl 2 -mediated FPA release from fibrinogen. In contrast, FEIBA fractions were able to split FPA from fibrinogen in the absence of CaCl 2 , indicating the presence of preformed thrombin in these fractions. The addition of CaCl 2 led to further thrombin generation, which could be prevented by high amounts of heparin or hirudin. Thus, in FC thrombin is either absent or blocked by the heparin added by manufacturers. However, rapid thrombin generation is observed upon incubation with CaCl 2 . The coagulant activity of FEIBA is due to preformed thrombin rather than to a “factor VIII inhibitor bypassing activity”.