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clinical application of platelet substitutes for control of post-cardiopulmonary bypass coagulopathy

Research Project

Project/Area Number 20K17734
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55030:Cardiovascular surgery-related
Research InstitutionNational Defense Medical College

Principal Investigator

Ishida Osamu  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 病院 外科, 講師 (20365266)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords血小板 / 人工血液 / 心臓血管外科 / 凝固障害 / 止血 / 人工血小板 / 血小板機能 / 人工心肺 / 凝固生涯 / 輸血 / 大量出血 / 輸血製剤
Outline of Research at the Start

心臓血管外科術後の大量出血は手術成績の悪化や医療費の負担増をもたらす。背景に複雑な未解明の病態があり、最終的な対策は輸血療法に頼らざるを得ない。心臓血管外科手術における輸血製剤使用量を減らすことは社会的にも求められるが、血液代替物の実用化は解決策となりうる。研究協力者らが開発したH12-(ADP)-リポソームは、完全合成による血小板代替物である。本研究においては、心臓血管外科術後出血制御を目的としたH12-(ADP)-リポソーム投与の臨床応用にむけた具体的な検討を行う。

Outline of Final Research Achievements

In order to prepare for the clinical application of H12-(ADP)-liposome administration, this study was conducted as a preliminary study for the clinical trial of H12-(ADP)-liposomes. The effect of H12-(ADP)-liposomes on coagulative function was investigated in vitro using perioperative blood samples from cardiovascular surgery patients with artificial heart-lungs. The results showed that H12-(ADP)-liposomes did not cause excessive platelet activation or hypercoagulable states and showed a certain degree of safety. The study has yielded useful results for the forthcoming clinical application of the world's first artificial platelet substitutes.

Academic Significance and Societal Importance of the Research Achievements

我が国では近い将来少子高齢化のため、献血に依存する血液製剤の不足が予想されるが、人工血液製剤は有効な代替物として期待される。人工血小板製剤H12-(ADP)-リポソーム投与は、心臓血管外科手術患者に重大な副作用を引き起こすことなく安全に使用できることが示唆された。本研究は、来る世界初の人工血小板製剤の臨床応用に向けた有益な成果をもたらした。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 2021 2020

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (4 results)

  • [Journal Article] In?vitro study on the effect of fibrinogen γ-chain peptide-coated ADP-encapsulated liposomes on postcardiopulmonary bypass coagulopathy using patient blood2023

    • Author(s)
      Ishida Osamu、Hagisawa Kohsuke、Yamanaka Nozomu、Nakashima Hiroyuki、Kearney Bradley M.、Tsutsumi Koji、Takeoka Shinji、Kinoshita Manabu
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 23 Issue: 7 Pages: 1934-1942

    • DOI

      10.1016/j.jtha.2023.03.018

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] H12-(ADP)-liposomes for hemorrhagic shock in thrombocytopenia: Mesenteric artery injury model in rabbits.2022

    • Author(s)
      Kohsuke Hagisawa, Manabu Kinoshita, Shinji Takeoka, Osamu Ishida, Yayoi Ichiki, Daizoh Saitoh, Morihiro Hotta, Masato Takikawa, Ivo P Torres Filho, Yuji Morimoto
    • Journal Title

      Research and practice in thrombosis and haemostasis

      Volume: 6 Issue: 2 Pages: e12659-e12659

    • DOI

      10.1002/rth2.12659

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Treatment of massive hemoptysis after thoracic aortic aneurysm repair.2022

    • Author(s)
      Morimura F, Hamamoto K, Edo H, Ishida O, Tsustsumi K, Tamada S, Kuwamura H, Enjoji Y, Suyama Y, Sugiura H, Watanabe S, Ozaki I, Shinmoto H.
    • Journal Title

      CVIR Endovasc.

      Volume: 5(1) Issue: 1 Pages: 17-17

    • DOI

      10.1186/s42155-022-00293-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Total aortic arch replacement using the J-graft open stent graft for distal aortic arch aneurysm: report from two centres in Japan.2021

    • Author(s)
      Tsutsumi K, Ishida O, Yamanaka N, Hayashi K, Hashizume K.
    • Journal Title

      Interact Cardiovasc Thorac Surg.

      Volume: 33(4) Issue: 4 Pages: 614-621

    • DOI

      10.1093/icvts/ivab114

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy of Resuscitative Infusion with Hemoglobin Vesicles in Rabbits with Massive Obstetric Hemorrhage2021

    • Author(s)
      Yukako Yuki, MD , Kohsuke Hagisawa, MD, PhD , Manabu Kinoshita, MD, PhD , Hiroki Ishibashi, MD , Kouki Kaneko, MD , Osamu Ishida, MD, PhD , Daizoh Saitoh, MD, PhD , Hiromi Sakai, PhD (Eng), PhD (Med Sci) , Katsuo Terui, MD, PhD
    • Journal Title

      American Journal of Obstetrics & Gynecology

      Volume: 224 Issue: 4 Pages: 398-398

    • DOI

      10.1016/j.ajog.2020.09.010

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic potential of fibrinogen γ-chain peptide-coated, ADP-encapsulated liposomes as a haemostatic adjuvant for post-cardiopulmonary bypass coagulopathy2020

    • Author(s)
      Ishida Osamu、Hagisawa Kohsuke、Yamanaka Nozomu、Tsutsumi Koji、Suzuki Hidenori、Takikawa Masato、Takeoka Shinji、Kinoshita Manabu
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 11308-11308

    • DOI

      10.1038/s41598-020-68307-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 臨床試験にむけたH12-(ADP)-リポソームのin vitro 安全性評価2023

    • Author(s)
      石田 治、萩沢康介、木下  学、武岡真司
    • Organizer
      ヒト細胞学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 臨床試験にむけたH12-(ADP)-リポソームのin vitro 安全性評価2022

    • Author(s)
      石田 治、萩沢康介、木下  学、武岡真司
    • Organizer
      日本血液代替物学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Therapeutic potential of H12-ADP-liposomes, as a synthetic platelet substitute, for post-cardiopulmonary bypass coagulopathy2020

    • Author(s)
      石田治、萩沢康介、山中望、堤浩二、木下学
    • Organizer
      日本循環器学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 人工血小板H12-(ADP)-リポソーム臨床試験の実現にむけて2020

    • Author(s)
      石田 治、萩沢康介、木下  学、武岡真司
    • Organizer
      血液代替物学会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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