Stable complex formation between serine protease inhibitor and zymogen: coagulation factor X cleaves the Arg393-Ser394 bond in a reactive centre loop of antithrombin in the presence of heparin.

Antithrombin (AT) inhibits several blood coagulation proteases, including activated factor X (FXa), by forming stable complexes with these proteases. Herein, we demonstrate that AT forms a stable complex with zymogen factor X (FX). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and size-exclusion chromatography analyses showed that AT and FX formed an SDS-stable complex, which is distinct in apparent molecular mass from an FXa-AT complex, in the presence of heparin.

Combining FVIIa and FX into a mixture which imparts a unique thrombin generation potential to hemophilic plasma: an in vitro assessment of FVIIa/FX mixture as an alternative bypassing agent.

Introduction: We previously reported that a combination of factors VIIa (FVIIa) and X (FX) might represent an effective and attractive alternative to recombinant factor VIIa (rFVIIa) and plasma-derived activated prothrombin complex concentrate (APCC) for controlling bleeding in hemophiliacs with inhibitors. The present study describes the standardization and preparation of a virus-inactivated and nano-filtrated plasma-derived FVIIa/FX concentrate. We hypothesized that the hemostatic capacity was equivalent to or better than current bypassing agents as evaluated by measurements of waveform APTT clotting and thrombin generation.