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

• Project/Area Number: 15K15658
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Hokkaido University
• Principal Investigator: Gando Satoshi 北海道大学, 医学研究院, 特任教授 (30125306)
• Co-Investigator(Renkei-kenkyūsha): SAWAMURA Atsushi 北海道大学, 大学院医学研究院, 特任准教授 (00241448) ; HAYAKAWA Mineji 北海道大学, 大学院医学研究院, 講師 (10374282) ; YANAGIDA Yuichiro 福岡市民病院, 救急科, 医員 (20455645) ; WADA Takeshi 北海道大学, 大学院医学研究院, 助教 (30455646) ; MIYAMOTO Daisuke 洞爺協会病院, 内科, 内科部長 (90750696)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 外傷 / 凝固線溶系 / 播種性血管内症候群（DIC / 播種性血管内症候群（DIC） / 凝固 / 線溶 / DIC / 出血

Outline of Final Research Achievements

To elucidate the mechanisms of trauma-induced coagulopathy, prospective and retrospective studies were performed. We demonstrated that trauma itself induces changes in coagulation and fibrinolysis, which consists of activation of coagulation (thrombin generation), insufficient anticoagulation systems (TFPI, antithrombin, protein C and thrombomodulin), and inhibition of fibrinolysis by PAI-1. The conditions are coincided with the pathophysiology of disseminated intravascular coagulation (DIC). These evidences were also confirmed by experimental studies using Noble-Collip Drum rat trauma models. Base on the results, we have published several original studies and review articles including one systematic review. To confirm these phenomenon, we, have conducted prospective multicenter study recruiting 108 institutes in Japan. The study has now completed and is waiting the publication of the obtained results in the English journal.

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: J Intensive Care Med Volume: - Issue: 5 Pages: 885066618761637-885066618761637
  • DOI: 10.1177/0885066618761637
  • Peer Reviewed / Open Access
• [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
  • 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
  • NAID: 120006382293
  • 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 Issue: 05 Pages: 851-859
  • DOI: 10.1160/th16-07-0547
  • NAID: 120006318738
  • 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 Issue: 1 Pages: 219-219
  • DOI: 10.1186/s13054-017-1808-9
  • Peer Reviewed / Open Access
• [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 Issue: 1 Pages: 110-110
  • 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 Issue: 4 Pages: 426-431
  • DOI: 10.1002/ams2.299
  • Peer Reviewed
• [Journal Article] Activated protein C does not increase in the early phase of trauma with disseminated intravascular coagulation: comparison with acute coagulopathy of trauma-shock. (2016)
  • Author(s): S. Jesmin, S. Gando, T. Wada, M. Hayakawa, A. Sawamura
  • Journal Title: Journal Intensive Care Volume: 4(4) Issue: 1 Pages: 1-1
  • DOI: 10.1186/s40560-015-0123-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock. (2016)
  • Author(s): 3.Fujishima S, Gando S, Daizoh S, Kushimoto S, Ogura H, Mayumi T, Takuma K, Kotani J, Yamashita N, Tsuruta R, Takeyama N, Shiraishi S, Araki T, Suzuki K, Ikeda H, Miki Y, Suzuki Y, Yamaguchi Y, Aikawa N.
  • Journal Title: Respirology Volume: 21 Issue: 5 Pages: 898-904
  • DOI: 10.1111/resp.12769
  • Peer Reviewed / Open Access
• [Journal Article] Antithrombin supplementation and risk of bleeding in patients with sepsis-associated disseminated intravascular coagulation (2016)
  • Author(s): Iba T, Gando S, Saitoh D, Wada H, Di Nisio M, Thachil J.
  • Journal Title: Thrombosis Research Volume: 145 Pages: 46-50
  • DOI: 10.1016/j.thromres.2016.07.016
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hemostasis and thrombosis in trauma patients. (2015)
  • Author(s): Gando S
  • Journal Title: Seminars in Thrombosis and Haemostasis Volume: 41 Issue: 01 Pages: 26-34
  • DOI: 10.1055/s-0034-1398378
  • Peer Reviewed / Open Access
• [Journal Article] Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock. (2015)
  • Author(s): Gando S, Otomo Y.
  • Journal Title: Critical Care Volume: 19 Issue: 1 Pages: 72-72
  • DOI: 10.1186/s13054-015-0735-x
  • Peer Reviewed / Open Access
• [Journal Article] Noble-Collip drum Trauma induces disseminated intravascular coagulation but not acute coagulopathy of trauma-shock. (2015)
  • Author(s): Hayakawa M, Gando S, Ono Y, Wada T, Yanagida Y, Sawamura A, Ieko M.
  • Journal Title: Shock Volume: 43 Issue: 3 Pages: 261-267
  • DOI: 10.1097/shk.0000000000000281
  • NAID: 120005712471
  • Peer Reviewed / Open Access
• [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
• [Presentation] Trauma, Shock, and disseminated intravascular coagulation. (2016)
  • Author(s): Gando S
  • Organizer: XXlllrd International Congresson Fibrinolysis and XVlth International Workshop on Molecular and Cellular Biobgy of Plasminogen Activation
  • Place of Presentation: 日本平ホテル (静岡、日本)
  • Year and Date: 2016-10-17
  • Int'l Joint Research / Invited
• [Presentation] DIC and fibrinolysis in patients with trauma and out-of-hospital cardiac arbest. (2016)
  • Author(s): Gando S, Wada T, Ono Y, Maekawa K, Katabami K, Hayakawa M, Sawamura A.
  • Organizer: The 9th Congress of Asian-Pacific Society on Thrombosis and Hemostasis
  • Place of Presentation: Taipei International Convention Center (Taipei, Taiwan)
  • Year and Date: 2016-10-06
  • Int'l Joint Research / Invited
• [Presentation] Disseminated intravascular coagulation during eary phase of out-of-hospital cardiac arrest and resuscitation belongs to the fibrinolytic phonotype. (2016)
  • Author(s): Sadamoto Y, Katabami K, Wada T, Ono Y, Maekawa K, Hayakawa M, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01
  • Int'l Joint Research
• [Presentation] Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with patients with out-of-hospital cardiac arrest. (2016)
  • Author(s): Kodate A, Katabami K, Wada T, Ono Y, Maekawa K, Hayakawa M, Sawamura A, Gando S
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01
  • Int'l Joint Research
• [Presentation] Trauma, shock, and disseminated intravascular coagulation. (2016)
  • Author(s): Gando S
  • Organizer: 3rd World Trauma Congress
  • Place of Presentation: Vigyan Bhawan (New Delhi, India)
  • Year and Date: 2016-08-17
  • Int'l Joint Research / Invited
• [Presentation] DIC in trauma. (2015)
  • Author(s): Gando S
  • Organizer: XXV Congress of the International Society on Thrombosis and Haemostasis and 61st Annual SSC Meeting, June 21, 2015 Toronto
  • Place of Presentation: Metro Tronto Convention Center (Tronto, Canada)
  • Year and Date: 2015-06-20
  • Int'l Joint Research / Invited
• [Presentation] Role of activated protein C and soluble fibrin in the early phase of trauma with disseminated intravascular coagulation: Comparison with acute coagulopathy of trauma-shock. (2015)
  • Author(s): Gando S
  • Organizer: XXV Congress of the International Society on Thrombosis and Haemostasis and 61st Annual SSC Meeting
  • Place of Presentation: Metro Tronto Convention Center (Tronto, Canada)
  • Year and Date: 2015-06-20
  • Int'l Joint Research
• [Presentation] Fibrinogenの低下を認めなくてもD-dimer高値は予後不良の指標である (2015)
  • Author(s): 早川峰司
  • Organizer: 第29回日本外傷学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター (北海道札幌市）
  • Year and Date: 2015-06-11
• [Presentation] J-OCTET報告 頭部単独外傷におけるTrauma-induced coagulopathyと組織低かん流 (2015)
  • Author(s): 早川峰司
  • Organizer: 第29回日本外傷学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2015-06-11
• [Presentation] Anticoagulation mechanisms are impaired in the early phase of trauma with DIC. (2015)
  • Author(s): Gando S
  • Organizer: 18th International Meeting of the Danubian League Against Thrombosis and Haemorrhagic Disorders
  • Place of Presentation: Hotel Radon Plaza (Bosnia and Herzegovina, Sarajevo)
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] Impaired coagulation mechanisms in trauma patients with disseminated intravascular coagulation and acute coagulopathy trauma-shock. (2015)
  • Author(s): Gando S
  • Organizer: 16th Annual NATA Symposium on Patient Blood Management, Haemostasis and Thrombosis
  • Place of Presentation: Prague Congress Centre, (Prague, Czechoslovakia)
  • Year and Date: 2015-04-16
  • Int'l Joint Research
• [Book] 新・血栓止血血管学 凝固と炎症 (2015)
  • Author(s): 一瀬白帝
  • Total Pages: 189
  • Publisher: 金芳堂