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The development of coagulation factor concentrate based on thrombin burst interaction between coagulation factors

Research Project

Project/Area Number 18K08823
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Ogawa Satoru  京都府立医科大学, 医学(系)研究科(研究院), 講師 (50636131)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
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)
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
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.

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。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2021 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results)

  • [Journal Article] Clotting time results are not interchangeable between EXTEM and FIBTEM on rotational thromboelastometry2020

    • Author(s)
      M. Judd, E. Strauss, S. Hasan, E. Abuelkasem, J. Li, S. Deshpande, M.A. Mazzeffi, Satoru Ogawa, KA. Tanaka
    • Journal Title

      J Cardiothorac Vasc Anesth

      Volume: 34 Pages: 1467-1473

    • Related Report
      2019 Research-status Report
  • [Journal Article] Whole Blood Point-of-care Testing for Incomplete Reversal with Idarucizumab in Supratherapeutic Dabigatran2020

    • Author(s)
      Shusuke Takeshita, Kenichi A. Tanaka, Teiji Sawa, Masashi Sanda, Toshiki Mizobe, Satoru Ogawa
    • Journal Title

      Anesthesia & Analgesia

      Volume: 130 Pages: 535-541

    • Related Report
      2019 Research-status Report
  • [Journal Article] Prohemostatic Activity of Factor X in combination with Activated Factor VII in Dilutional Coagulopahty2019

    • Author(s)
      Shusuke Takeshita, Satoru Ogawa, Yoshinobu Nakayama, Nobuhiro Mukai, Yasufumi Nakajima, Toshiki Mizobe, Teiji Sawa, Kenichi A. Tanaka
    • Journal Title

      Anesthesia & Analgesia

      Volume: 129 Pages: 339-345

    • Related Report
      2019 Research-status Report
  • [Journal Article] Prohemostatic Activity of Factor X in Combination With Activated Factor VII in Dilutional Coagulopathy.2018

    • Author(s)
      Takeshita S, Ogawa S, Nakayama Y, Mukai N, Nakajima Y, Mizobe T, Sawa T, Tanaka KA.
    • Journal Title

      Anesth Analg.

      Volume: 印刷中 Issue: 2 Pages: 339-345

    • DOI

      10.1213/ane.0000000000003858

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 外科周術期管理に関連した血小板・血液凝固領域における最新の知見2018

    • Author(s)
      小川覚, 竹下秀祐
    • Journal Title

      日本臨床麻酔誌

      Volume: 38 Pages: 519-530

    • NAID

      130007468193

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 心臓血管麻酔における血液粘弾性検査の使用指針」を読み解く2021

    • Author(s)
      小川覚
    • Organizer
      第26回日本心臓血管麻酔学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Point-of-care Coagulation Monitoring in Cardiac Surgery2019

    • Author(s)
      Satoru Ogawa
    • Organizer
      The 96th Annual Scientific Meeting of the Korean Society of Anesthesiologists, Seoul, South Korea
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Point-of-care Coagulation Monitoring in Cardiovascular Surgery2019

    • Author(s)
      Satoru Ogawa
    • Organizer
      The 17th International Congress of Cardiothoracic and Vascular Anesthesia, Seoul, South Korea
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 大量出血症例に対する血液製剤の適正な使用ガイドラインを考える.「フィブリノゲン製剤・クリオプレシピテートの使用について」2019

    • Author(s)
      小川覚
    • Organizer
      第24回日本心臓血管麻酔学会 学術集会、京都市
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 経口抗凝固薬に対する拮抗治療の最前線2018

    • Author(s)
      小川覚
    • Organizer
      第46回日本集中治療医学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 術中大量出血と凝固因子補充療法2018

    • Author(s)
      小川覚
    • Organizer
      臨床検査技師会輸血検査講演会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2023-01-30  

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