Platelet substitute for post cardiopulmonary bypass coagulopathy

• Project/Area Number: 18K16407
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: National 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): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 人工血液 / 血小板 / 人工心肺 / 凝固障害 / 心臓血管外科手術 / 心臓血管外科 / 人工血小板 / 心臓外科手術 / 人工心肺後凝固障害

Outline of Final Research Achievements

The use of blood transfusion products in cardiovascular surgery is very large. While there is a societal demand to reduce this, the practical application of the platelet substitute, H12-(ADP)- liposomes, could be one solution. A rabbit model of post-cardiopulmonary bypass coagulopathy was created and administration experiments were conducted, it was shown that H12-(ADP)-liposomes promoted platelet aggregation at the site of tissue injury and shortened hemostatic thrombus formation time. In this preclinical phase experiment, it was suggested that H12-(ADP)-liposome may reduce platelet transfusion volume after cardiovascular surgery.

Academic Significance and Societal Importance of the Research Achievements

心臓外科手術における術後出血は血小板機能障害、消費性凝固障害等が複雑に関連して生じる人工心肺後凝固障害と言われる病態が背景にある。これを制御し輸血使用量を低減させることが出来れば、少子高齢化を迎え献血による輸血製剤が近い将来に不足する見通しである我が国では大きな意義がある。今回心臓手術後と限られた領域であるが血小板代替物であるH12-(ADP)-リポソームの有用性を明らかにし、臨床応用への基礎データを得ることが出来た。

Research Products

• [Presentation] A synthetic platelet substitute for post cardiopulmonary bypass coagulopathy (2019)
  • Author(s): Osamu Ishida, Kosuke Hagisawa, Nozomu Yamanaka, Koji Tsutsumi, Manabu Kinoshita
  • Organizer: 2019 Military Health System Research Symposium
  • Int'l Joint Research
• [Presentation] Therapeutic Potential of Fibrinogen ganmma‐Chain Peptide‐Coated, ADP‐Encapsulated Liposomes, as a Synthetic Platelet Substitute, for Post-Cardiopulmonary Bypass Coagulopathy (2019)
  • Author(s): Osamu Ishida, Kohsuke Hagisawa, Nozomu Yamanaka, Koji Tsutsumi, Hidenori Suzuki, Shinji Takeoka and Manabu Kinoshita
  • Organizer: 17th International Symposium on Blood Substitutes & Oxygen Therapeutics
  • Int'l Joint Research
• [Presentation] 人工血小板による人工心肺後凝固障害の制御 (2019)
  • Author(s): 石田 治、堤 浩二、田口眞一
  • Organizer: 日本心臓血管外科学会
• [Presentation] 再現性の高い人工心肺動物モデルの作成法 (2018)
  • Author(s): 石田 治、堤 浩二、田口眞一
  • Organizer: 日本胸部外科学会総会
• [Presentation] 人工血小板H12-(ADP)-リポソームによる人工心肺後凝固障害の制御、前臨床段階における評価 (2018)
  • Author(s): 石田 治、萩沢康介、鈴木英紀、木下 学
  • Organizer: 血液代替物学会