Genomic polymorphisms of disseminated intravascular coagulation in patients with trauma and sepsis.

2016 Fiscal Year Annual Research Report

• Project/Area Number: 25293364
• Research Institution: Hokkaido University
• Principal Investigator: 丸藤 哲 北海道大学, 医学(系)研究科(研究院), 特任教授 (30125306)
• Co-Investigator(Kenkyū-buntansha): Jesmin Subrina 筑波大学, 体育系, 研究員 (60374261)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 外傷 / 敗血症 / DIC / 臓器不全

Outline of Annual Research Achievements

国際共同研究提携先であるバングラデシュ国ボグラ大学で検体収集実務担当者の異動があり、さらに同大学でICU新規開設が予定された。この二つの理由により外傷および敗血症症例の研究検体収集が一時頓挫した。ICU開設を待つ期間に、外傷および敗血症と同様の生体反応を引き起こす心停止・蘇生（虚血/再灌流障害）症例での研究を進めた。心停止・蘇生で易血栓性DICが起こる事は既に証明して公表しているが、その前段階のDICに関する研究を行い、凝固亢進（易血栓性）に到る前に線溶亢進が起こることを解明した。すなわち、心停止・蘇生に伴い血管内皮細胞が低酸素・虚血に陥るが、この刺激により血管内皮細胞Weibel Palde小体からtissue-type plasminogen activator (t-PA)が遊離し、フィブリン・フィブリノゲン分解が起こる。この結果血中FDP/D-dimerが高値となることが判明し、線溶亢進型　DICが引き起こされる。このDICは易血栓性を持つ線溶抑制型DICに移行することを証明した。この両DICにより全身性炎症反応症候群、多臓器不全が惹起され、これらがDIC発症症例の予後を不良としていることを証明した。この研究成果は国際学会で発表し、さらに論文としてThrombosis Research誌（易血栓性DIC）およびThrombosis Journal誌(易血栓性に到る全段階の線溶亢進型DIC)で発表した。2017年初頭にボグラ大学からICU開設の報告があり、現在外傷および敗血症の易血栓性DICに関する研究を再開続行中である。研究期間は終了したが、他の競争的資金を使用して研究完遂を目指している

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] Grameen Health and Grameen Bank/Trauma Center, Mirpur, Dhaka/Rajshahi Medical College and Hospital(バングラデシュ)
  • Country Name: BANGLADESH
  • Counterpart Institution: Grameen Health and Grameen Bank/Trauma Center, Mirpur, Dhaka/Rajshahi Medical College and Hospital
  • # of Other Institutions: 3
• [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): Jesmin S, Gando S, Wada T, Hayakawa M, Sawamura A.
  • Journal Title: Journal of Intensive Care Volume: 4 Pages: 1
  • DOI: 10.1186/s40560-015-0123-2
  • Peer Reviewed / Open Access
• [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 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
• [Journal Article] Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest. (2016)
  • Author(s): Wada T, Gando S, Ono Y, Maekawa K, Katabami K, Hayakawa M, Sawamura A.
  • Journal Title: Thrombosis Journal Volume: 14 Pages: 43
  • DOI: 10.1186/s12959-016-0116-y
  • Peer Reviewed / Open Access
• [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 (静岡県、静岡市)
  • Year and Date: 2016-10-17 – 2016-10-21
  • Int'l Joint Research / Invited
• [Presentation] DIC and fibrinolysis in patients with trauma and out-of-hospital cardiac arbest (2016)
  • Author(s): 2.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 – 2016-10-09
  • 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 the European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01 – 2016-10-05
  • 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 the European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01 – 2016-10-05
  • 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 – 2016-08-20
  • Int'l Joint Research / Invited