Pathogenesis of hyperfibrinolysis to fibrinolytic suppression in acute phase of trauma

Research Project

Project/Area Number	18K08905
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55060:Emergency medicine-related
Research Institution	Hokkaido University
Principal Investigator	Hayakawa Mineji 北海道大学, 大学病院, 准教授 (10374282)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	外傷 / 凝固障害 / 線溶 / 播種性血管内凝固症候群 / 凝固活性化 / 線溶亢進 / 鈍的外傷 / 播種性血管内凝固
Outline of Final Research Achievements	Immediately after trauma, the total tissue-plasminogen activator (tPA) level significantly increased in plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) in plasma significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 minutes after trauma returned quickly to levels comparable to those in the control group. in conclusions, fibrinolytic activation was observed only immediately after trauma. After trauma, production of both of t-PA and PAI-1 increased gradually in various organs. However, only plasma PAI-1 levels increased exponentially, and plasma tPA levels 60 and 180 minutes after trauma were the same as those before the trauma. Therefore, immediately after trauma, the fibrinolytic system was activated, but its activation was quickly and intensely suppressed.
Academic Significance and Societal Importance of the Research Achievements	外傷直後の線溶系の変動を詳細に解明することが出来た。この病態の解明により、現在広く行われている重症外傷直後の抗線溶薬の投与方法に関して、①早期投与は妥当であること。②その後の長時間にわたる持続投与は不要である可能性があることが、示された。今後のさらなる検討により、適切な抗線溶薬の投与方法が明らかになるかもしれない。