The development of coagulation factor concentrate based on thrombin burst interaction between coagulation factors
| Project/Area Number |
18K08823
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55050:Anesthesiology-related
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Ogawa Satoru 京都府立医科大学, 医学(系)研究科(研究院), 講師 (50636131)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 血液凝固 / 止血異常 / 輸血 / 血栓症 / 凝固因子 / 凝固障害 / 血液凝固因子 / 血液希釈 / トロンビン / 周術期 / 大量出血 / 止血 / 心臓外科手術 |
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| Outline of Final Research Achievements |
After severe hemodilution, the decrease of thrombin generation is caused by the multiple loss of procoagulant factors. We hypothesized that the combination of FX with FVIIa (FVIIa/FX) could improve prohemostatic activity of recombinant activated factor FVII (FVIIa) in dilutional coagulopathy. In diluted plasma, the addition of either FVIIa/FX or rFVIIa shortened the lag time and increased the peak thrombin generation (TG), but FVIIa/FX at 0.35 μg/mL was more effective than rFVIIa at 6.4 μg/mL. In thromboelastometry, FVIIa/FX restored the clotting time most efficiently. FVIIa/FX facilities the initiation of TG more efficiently than rFVIIa alone in dilutional coagulopathy. The combination of FX may reduce the requirement of FVIIa in cardiac surgery.
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| Academic Significance and Societal Importance of the Research Achievements |
血液希釈下において十分な第X因子が存在することで効率的な第VII因子によるトロンビン生成が可能であった。遺伝子組み換え活性型FVII因子製剤に対するFVIIa/FXの優位性は、血友病患者における活性型FVII製剤における臨床使用濃度に比較しても低い濃度でも明らかであった。このことは、凝固カスケード上で主要な凝固因子を少量で組み合わせる事で、不必要な酵素誘導に起因した血栓性合併症を低下できることを示唆している。今後、第II因子、 第V因子、第VII因子、第X因子に着目して、新規混合物を作成することで、新たな凝固因子濃縮製剤の開発の足がかりとしたい。
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Report
(5 results)
Research Products
(11 results)
