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Studies on the mechanisms of activation and inactivation of factor VIII: Applications of novel (anti-)coagulant therapy

Research Project

Project/Area Number 15K09663
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNara Medical University

Principal Investigator

Nogami Keiji  奈良県立医科大学, 医学部, 准教授 (50326328)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords第VIII因子 / トロンビン / 活性型第VII因子 / 組織因子 / 凝固機序 / 活性化 / 第X因子 / FVIII / FVIIa / 内因系 / 外因系 / 結合領域 / 血液凝固 / 活性化第VII因子 / 活性化/不活化
Outline of Final Research Achievements

Regards the coagulant factor (F)VIII protein that is essential to both sides of hemorrhage and hemostasis in the blood coagulation, we for the first time identified the thrombin-binding sites responsible for the cleavages at Arg372 and Arg1689 in the FVIII activation. In addition, in terms of activated FVII/tissue factor (FVIIa/TF), we found not only the extrinsic-related coagulation mechanism, the intrinsic-related coagulation mechanism by the FVIII-FVIa/TF-related regulation exerts, consequently both mechanisms function in the initial phase of coagulation process.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results,  Acknowledgement Compliant: 5 results) Presentation (6 results) Book (1 results)

  • [Journal Article] Factor (F)VIII/VIIa enhances global haemostatic function in the co-presence of bypassing agents and FVIII among patients with haemophilia A with inhibitor2018

    • Author(s)
      Nogami K, Matsumoto T, Yada K, Ogiwara K, Furukawa S, Shida Y, Takeyama M, Shima M
    • Journal Title

      Br J Haematol

      Volume: ahead of printing Issue: 4 Pages: 528-536

    • DOI

      10.1111/bjh.15209

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors.2017

    • Author(s)
      Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Kasai R, Yoneyama K, Yoshida H, Nogami K.
    • Journal Title

      Blood Adv.

      Volume: 1(22) Issue: 22 Pages: 1891-1899

    • DOI

      10.1182/bloodadvances.2017006684

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful prophylaxis using activated prothrombin complex concentrates (aPCC) in a severe haemophilia A patient with inhibitor previously unresponsive to on-demand daily infusions of aPCC.2017

    • Author(s)
      Furukawa S, Nogami K, Ogiwara K, Yada K, Shima M.
    • Journal Title

      Haemophilia.

      Volume: 23 Issue: 5

    • DOI

      10.1111/hae.13310

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The utility of thromboelastography in inherited and acquired bleeding disorders.2016

    • Author(s)
      Keiji Nogami
    • Journal Title

      British Journal of Haematology

      Volume: 174(4) Pages: 503-514

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Assessing the clinical severity of type 1 von Willebrand disease patients with a microchip flow-chamber system.2016

    • Author(s)
      Nogami K, Ogiwara K, Yada K, Shida Y, Takeyama M, Yaoi H, Minami H, Furukawa S, Hosokawa K, Shima M.
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 14(4) Pages: 667-674

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A new parameter in the thrombin generation assay, mean velocity to peak thrombin, reflects factor VIII activity in patients with haemophilia A2016

    • Author(s)
      Takeyama M, Nogami K, Shima M.
    • Journal Title

      Haemophilia

      Volume: 22(5) Pages: 474-477

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Phenotypic heterogeneity of hemostasis in severe hemophilia2015

    • Author(s)
      Nogami K, Shima M.
    • Journal Title

      Seminars in Thrombosis and Hemostasis

      Volume: 41 Pages: 826-831

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Systematic monitoring of hemostatic management in hemophilia A patients with inhibitor in the perioperative period using rotational thromboelastometry.2015

    • Author(s)
      Furukawa S, Nogami K, Ogiwara K, Yada K, Minami H, Shima M.
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 13 Pages: 1279-1284

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mild hemophilia A patient with novel Pro1809Leu mutation develops an anti-C2 antibody inhibiting allogeneic but not autologous factor VIII activity.2015

    • Author(s)
      Yada K, Nogami K, Takeyama M, Ogiwara K, Wakabayashi H, Shima M.
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 13 Pages: 1843-1853

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 第VIII因子A1残基346-349はArg372の開裂を制御する新たなトロンビン結合部位である2017

    • Author(s)
      南博明, 野上恵嗣, 笹井香那, 古川晶子, 武山雅博, 嶋緑倫
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 凝固初期相におけるFVIII活性化を介したTF依存性内因系tenase促進機序2017

    • Author(s)
      古川晶子, 野上恵嗣, 荻原建一, 嶋緑倫
    • Organizer
      第39回日本血栓止血学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Tenase(Xase) 反応軸に基づく中等症・軽症血友病Aにおける異常FVIIIの多元的機能解析2017

    • Author(s)
      矢田弘史, 野上恵嗣, 竹中亜利沙, 河村武志, 嶋緑倫
    • Organizer
      第39回日本血栓止血学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血液凝固第VII因子の軌跡と今後の展望2017

    • Author(s)
      野上恵嗣
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 包括的ダイナミック解析による血友病の凝固線溶動態の特性2017

    • Author(s)
      松本智子, 野上恵嗣, 笹井香那, 荻原建一, 竹中亜利沙, 嶋緑倫
    • Organizer
      第39回日本血栓止血学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A novel mechanism on thrombin-catalyzed activation of factor VIII molecule during the clot formation2016

    • Author(s)
      Keiji Nogami
    • Organizer
      第38回日本血栓止血学会学術集会 SPCシンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Book] 第VIII因子と第V因子の基礎と臨床 新・血栓止血血管学 凝固と炎症2015

    • Author(s)
      野上恵嗣
    • Total Pages
      13
    • Publisher
      金芳堂
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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