| Project/Area Number |
20K09280
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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 55060:Emergency medicine-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Gando Satoshi 北海道大学, 医学研究院, 名誉教授 (30125306)
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| Co-Investigator(Kenkyū-buntansha) |
和田 剛志 北海道大学, 大学病院, 助教 (30455646)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 外傷 / 自然免疫反応 / 凝固線溶反応 / 播種性血管内凝固症候群（DIC） / 凝固障害 / 凝固 / 線溶 / 播種性血管内凝固症候群 / ヒストン |
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| Outline of Research at the Start |
本研究は、
1）DAMPs（histone）とNETsが共同して外傷性DICを引き起こす事を証明する事、
2）外傷初期（線溶亢進型）・後期（線溶抑制型）DICいずれもhistone/NETsによる全身性トロンビン産生が持続する事、
3）生理的凝固制御薬（アンチトロンビン）による治療介入が外傷性DICの予後を改善する事、の証明である。
即ち、histone/NETsを標的とした外傷性DICの最新の病態生理の解明と治療法の確立を目指す。
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| Outline of Final Research Achievements |
Review article on the relationship between trauma-induced coagulopathy and disseminated intravascular coagulation (DIC) has been published through the debate in the International Society on Thrombosis and Haemostasis. This review article demonstrated that severe trauma-induced coagulopathy can progress to DIC in the early stage of trauma. During these processes, we have published 4 articles related to DIC in trauma patients regarding 1) intravascular thrombin generation in DIC, 2) effects of antithrombin on the thrombin generation, development of multiple organ dysfunction syndrome (MODS), and mortality in DIC, 3) prediction of massive transfusion, MODS, and hospital mortality by the development of DIC and DIC score, and 4) tranexamic acid-induced reduction of fibrinolysis and fibrinogenolysis. Histones- and neutrophil extracellular traps (NETs)-participated pathophysiology of trauma-induced coagulopathy and DIC was discussed and has been published as a review article.
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| Academic Significance and Societal Importance of the Research Achievements |
外傷性凝固障害と外傷に起因するDICの関連に関する長年の議論を国際血栓止血学会が取り纏めた社会的意義は非常に高い。取り纏め過程で、外傷症例において多臓器機能障害発症を介して予後に大きな影響を与えるDICの発症機序が、血管内トロンビン産生とアンチトロンビン減少、およびトラネキサム酸投与の観点から解明され、その病態生理にDamage-associated molecular patterns (DAMPs)として知られるHistone/NETsが関与する事を総説としてまとめ得た学術的意義は大きい。
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