Pathophysiology of coagulation and fibrinolysis at an early phase of trauma.

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15K15658
• Research Institution: Hokkaido University
• Principal Investigator: 丸藤 哲 北海道大学, 医学研究院, 特任教授 (30125306)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 外傷 / 凝固線溶系 / 播種性血管内症候群（DIC）

Outline of Annual Research Achievements

外傷後の凝固線溶動態解明を目的とした研究を前向き基礎・臨床および後ろ向き臨床研究として実施した。欧米では希釈・低体温・アシドーシスが外傷後凝固線溶系変化の本態と考えられてきたが、これらの原因以外に外傷自体が引き起こす凝固線溶系変化があることが半世紀前から知られている。すなわち、重症外傷では生理的止血・創傷治癒過程が破綻し病的凝固線溶系変化が起こる。この病態は凝固亢進、凝固制御機能不全、線溶抑制であり、播種性血管内凝固症候群（disseminated intravascular coagulation, DIC）の病態生理に一致する事をNoble-Collip drum shockモデルおよび組織因子静注モデルを使用した基礎実験で確認した。この成果をこれまでの教室の研究内容と合わせて数本の英文総説および英文原著論文として公表した。さらに、重症単独頭部外傷での凝固線溶動態を合わせて検討した。この研究で重症頭部外傷初期は線溶亢進型DICが起こる事を証明して英文原著論文として公表した。これらの結果を臨床症例で確認するために、前向き多施設共同研究を北海道大学救急医学教室（研究者代表者所属）が研究主管校として実施した。2016年4月から症例登録を参加108施設で開始して2017年11月に529症例（285変数）を収集して終了した。2018年3月に一次クレンジングを終了、4月中に二次クレンジングを終了、5月に固定データセットを公開する。その後解析を開始し、2018年11月の日本救急医学会学術集会および海外関連学会（2019年Society of Critical Care Medicine, International Society on Thrombosis and Haemostasis）で発表する。同時進行で英文論文執筆を開始し、速やかに英文原著論文として世界に公表予定である。

Research Products

• [Journal Article] Complementary Role of Hypothermia Identification to the Quick Sequential Organ Failure Assessment Score in Predicting Patients With Sepsis at High Risk of Mortality: A Retrospective Analysis From a Multicenter, Observational Study. (2018)
  • Author(s): Kushimoto S, Gando S, Ogura H, Umemura Y, Saitoh D, Mayumi T, Fujishima S, Abe T, Shiraishi A, Ikeda H, Kotani J, Miki Y, Shiraishi SI, Suzuki K, Suzuki Y, Takeyama N, Takuma K, Tsuruta R, Yamaguchi Y, Yamashita N, Aikawa N
  • Journal Title: Journal of Intensive Care Medicine Volume: 1 Pages: 885066618761637
  • DOI: 10.1177/0885066618761637
  • Peer Reviewed
• [Journal Article] Activated protein C plays no major roles in the inhibition of coagulation or increased fibrinolysis in acute coagulopathy of trauma-shock: a systematic review. (2018)
  • Author(s): Gando S, Mayumi T, Ukai T
  • Journal Title: Thrombosis Jornal Volume: in press Pages: in press
  • Peer Reviewed
• [Journal Article] Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients. (2017)
  • Author(s): Ono Y, Hayakawa M, Maekawa K, Kodate A, Sadamoto Y, Tominaga N, Murakami H, Yoshida T, Katabami K, Wada T, Sageshima H, Sawamura A, Gando S
  • Journal Title: Resuscitation Volume: 117 Pages: 62-67
  • DOI: 10.1016/j.resuscitation.2016.11.017
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of recombinant human soluble thrombomodulin in disseminated intravascular coagulation patients with acute renal dysfunction. (2017)
  • Author(s): Hayakawa M, Kushimoto S, Watanabe E, Goto K, Suzuki Y, Kotani T, Kiguchi T, Yatabe T, Tagawa J, Komatsu F, Gando S
  • Journal Title: Thromb Haemost Volume: 117 Pages: 851-859
  • DOI: 10.1160/TH16-07-0547
  • Peer Reviewed
• [Journal Article] Disseminated intravascular coagulation with increased fibrinolysis during the early phase of isolated traumatic brain injury. (2017)
  • Author(s): Wada T, Gando S, Maekawa K, Katabami K, Sageshima H, Hayakawa M, Sawamura A
  • Journal Title: Crit Care Volume: 21 Pages: 219
  • DOI: 10.1186/s13054-017-1808-9
  • Peer Reviewed
• [Journal Article] Effects of combination therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation. (2017)
  • Author(s): Iba T, Hagiwara A, Saitoh D, Anan H, Ueki Y, Sato K, Gando S
  • Journal Title: Ann Intensive Care Volume: 7 Pages: 110
  • DOI: 10.1186/s13613-017-0332-z
  • Peer Reviewed
• [Journal Article] Early evaluation of severity in patients with severe sepsis: a comparison with "septic shock" - subgroup analysis of the Japanese Association for Acute Medicine Sepsis Registry (JAAM-SR). (2017)
  • Author(s): Tarui T, Yamaguchi Y, Suzuki K, Tsuruta R, Ikeda H, Ogura H, Kushimoto S, Kotani J, Shiraishi SI, Suzuki Y, Takuma K, Takeyama N, Fujishima S, Mayumi T, Miki Y, Yamashita N, Aikawa N, Gando S
  • Journal Title: Acute Med Surg Volume: 27 Pages: 426-431
  • DOI: 10.1002/ams2.299
  • Peer Reviewed
• [Presentation] Trauma-induced coagulopathy and disseminated intravascular coagulation. (2017)
  • Author(s): Gando S
  • Organizer: The 26th International Society on Thrombosis and Hemostasis 2017 Congress
  • Invited
• [Presentation] Disseminated intravascular coagulation during early phase of isolated traumatic brain injury. (2017)
  • Author(s): Gando S, Sawamura A, Hayakawa M, Wada T, Yanagida Y, Miyamoto D, Maekawa K, Ono Y, Mizugaki A, Jesmin S.
  • Organizer: The 26th International Society on Thrombosis and Hemostasis 2017 Congress
  • Invited
• [Presentation] Trauma induced coagulopathy. (2017)
  • Author(s): Gando S
  • Organizer: Chinese Critical Care Congress 2017
  • Invited
• [Presentation] Disseminated intravascular coagulation during the early stage of isolated traumatic brain injury. (2017)
  • Author(s): Katabami K, Itagaki Y, Tsuchida T, Tomita A, Honma Y, Mizugaki A, Murakami H, Yoshida T, Oyasu T, Saito T, Wada T, Maekawa K, Sageshima H, Hayakawa M, Sawamura A, Gando S
  • Organizer: 30th Annual Congress of European Society of Intensive Care Medicine
• [Presentation] Effects of fibrinolysis and lactate on outcome in isolated traumatic brain injury with disseminated intravascular coagulation. (2017)
  • Author(s): Katabami K , Itagaki Y, Tsuchida T, Tomita A, Honma Y, Mizugaki A, Murakami H, Yoshida T, Oyasu T, Saito T, Wada T, Maekawa K, Sageshima H, Hayakawa M, Sawamura A, Gando S
  • Organizer: WFSICCM World Federation of Societies of Intensive and Critical Care Medicine 13th World Congress
• [Presentation] Disseminated intravascular coagulation during the early stage of isolated traumatic brain injury. (2017)
  • Author(s): Kenichi K, Itagaki Y, Tsuchida T, Tomita A, Honma Y, Mizugaki A, Murakami H, Yoshida T, Oyasu T, Saito T, Wada T, Maekawa K, Sageshima H, Hayakawa M, Sawamura A, Gando S
  • Organizer: WFSICCM World Federation of Societies of Intensive and Critical Care Medicine 13th World Congress, November 2017
• [Presentation] Low-perfusion pressure-induced tissue hypoperfusion does not contribute to hyperfibrinolysis in disseminated intravascular coagulation associated with isolated traumatic brain injury. (2017)
  • Author(s): Kenichi K, Itagaki Y, Tsuchida T, Tomita A, Honma Y, Mizugaki A, Murakami H, Yoshida T, Oyasu T, Saito T, Wada T, Maekawa K, Sageshima H, Hayakawa M, Sawamura A, Gando S
  • Organizer: WFSICCM World Federation of Societies of Intensive and Critical Care Medicine 13th World Congress, November 2017, Rio de Janeiro