The effects of physiological coagulation inhibitors and inflammation / aging on anticoagulant therapies

• Project/Area Number: 15K09068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Niigata University
• Principal Investigator: Izumi Daisuke 新潟大学, 医歯学系, 助教 (30529699)
• Co-Investigator(Kenkyū-buntansha): 佐藤 光希 新潟大学, 医歯学総合病院, 助教 (40600044)
• Co-Investigator(Renkei-kenkyūsha): SUDA Masayoshi 新潟大学, 医歯学総合病院, 医員 (70714509)
• Research Collaborator: FUSE Ichiro
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 抗凝固療法 / 直接型経口抗凝固薬 / ワルファリン / DOAC / 生理的凝固阻止因子 / NOAC / 血管内皮結合型組織因子経 路インヒビター / プロトロンビンフラグメント1+2 / 血管内皮結合型組織因子経路インヒビター

Outline of Final Research Achievements

The major findings of the present study were as follows: (1) direct oral anticoagulants (DOACs) effectively decreased thrombin generation at both the trough and peak concentration times, although the reduction of thrombin generation by DOACs was smaller than that achieved by warfarin treatment in the therapeutic range. (2) Patients on DOAC treatment showed a greater increase of thrombin generation after vascular injury than patients on warfarin treatment. (3) DOAC treatment had a more favorable effect on physiological coagulation inhibitors than warfarin treatment. These results suggest that, in contrast to warfarin treatment, DOAC treatment preserves thrombin generation in response to vascular injury and maintains protein C, protein S, and factor VII levels, which could partly explain the lower risk of hemorrhagic complications and thromboembolic events in patients using these anticoagulants.

Research Products

• [Journal Article] Effects of direct oral anticoagulants at the peak phase, the trough phase, and after vascular injury (2018)
  • Author(s): Otuki S, Izumi D, Suda M, Sato A, Hasegawa Y, Yagihara N, Iijima K, Chinushi M, Fuse I, Minamino T
  • Journal Title: J Am Coll Cardiol. Volume: 71 Issue: 1 Pages: 102-104
  • DOI: 10.1016/j.jacc.2017.10.076
  • Peer Reviewed / Open Access
• [Journal Article] Inappropriate inhibition of biventricular pacing due to diaphragmatic myopotentials amplified by the selectable sensing filter. (2017)
  • Author(s): Iijima K, Ishida N, Izumi D, Minamino T.
  • Journal Title: Europace. Volume: 印刷中 Issue: 12 Pages: 2014-2014
  • DOI: 10.1093/europace/euw372
  • Peer Reviewed / Open Access
• [Journal Article] 脳梗塞と抗凝固療法 (2017)
  • Author(s): 和泉 大輔
  • Journal Title: 新潟医学会雑誌 Volume: 131 Pages: 396-401
• [Journal Article] Manifestation of Latent Left Ventricular Outflow Tract Obstruction in the Acute Phase of Takotsubo Cardiomyopathy. (2016)
  • Author(s): Otuki S, Hasegawa K, Watanabe H, Katsuumi G, Yagihara N, Iijima K, Sato A, Izumi D, Furushima H,Chinushi M,Aizawa Y, and Minamino T.
  • Journal Title: Journal of Electrocardiology, Volume: - Issue: 3 Pages: 277-281
  • DOI: 10.1016/j.jelectrocard.2016.09.005
  • NAID: 130005171736
  • Peer Reviewed / Open Access
• [Journal Article] 心房細動治療と抗凝固薬 (2016)
  • Author(s): 和泉大輔
  • Journal Title: 柏崎市刈羽郡医師会報 Volume: 561 Pages: 3-9
• [Presentation] Early repolarization and risk of lone atrial fibrillation (2016)
  • Author(s): Yuki Hasegawa, Motoi Yuzawa, Hiroshi Watanabe, So Otsuki, Kenichi Iizima, Nobue Yagihara, Akinori Sato, Daisuke Izumi, and Tohru Minamino
  • Organizer: American Heart Association’s Scientific Sessions 2016
  • Place of Presentation: New Orleans, United States of America
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Comparisons of the effect of anticoagulation therapies on the coagulation system including the tissue factor pathway -The augmentation of tissue factor pathway inhibitors by the factor Xa inhibitors- (2016)
  • Author(s): Sou Otuki, Daisuke Izumi, Masayoshi Suda, Akinori Sato, Toshiki Takano, Yuki Hasegawa, Nobue Yagihara, Hiroshi Watanabe, Masaomi chinushi, Tohru Minamino
  • Organizer: The 80th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Sendai International Center, Tohoku University Centennial Hall, Sendai Civic Auditorium, Sendai, Japan
  • Year and Date: 2016-03-18
• [Presentation] Comparisons of the effect of anticoagulation therapies on the coagulation system including the tissue factor pathway between vitamin K antagonist and the factor Xa inhibitors (2015)
  • Author(s): Sou Otuki, Daisuke Izumi, Masayoshi Suda, Akinori Sato, Toshiki Takano, Yuki Hasegawa, Nobue Yagihara, Hiroshi Watanabe, Masaomi chinushi, Tohru Minamino
  • Organizer: ESC congress 2015
  • Place of Presentation: London, UK
  • Year and Date: 2015-08-29