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

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• 作者：Yasushi Nakatomi ; Teruhisa Nakashima ; Soutaro Gokudan ; Hiroki Miyazaki ; Manami Tsuji ; Takako Hanada-Dateki ; Tatsuya Araki ; Kazuhiko Tomokiyo ; Takayoshi Hamamoto ; Yoichi Ogata
• 关键词：FVIIa ; FX ; hemophilia ; bypassing agents ; inhibitors ; APCC
• 刊名：Thrombosis Research
• 出版年：2010
• 出版时间：May 2010
• 年：2010
• 卷：125
• 期：5
• 页码：457-463
• 全文大小：1068 K

文摘

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.

Results

Kinetic analyses showed that a ""normal"" FX concentration of approximately 140 nM in plasma did not induce maximum catalytic efficacy of FVIIa and that an increase in the concentration of FX in hemophilic plasma enhanced the thrombin generation potential of FVIIa. Thus, the FVIIa/FX mixture was prepared by assembling plasma-derived FVIIa and FX at a weight ratio of 1:10. The FVIIa/FX mixture proved superior to rFVIIa with regards to shortening the APTT and accelerating the thrombin generation in hemophilic plasma. The FVIIa/FX mixture promoted the generation of thrombin more than did rFVIIa.

Conclusions

Increasing the FX concentration in hemophilic plasma gives a higher clotting potential of FVIIa. A FVIIa/FX concentrate may serve as a new alternative bypassing agent.