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Basic reserch on hemostasis to establish a novel hemostatic therapy for hemophilia A patients with inhibitors

Research Project

Project/Area Number 25860878
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

YADA Koji  奈良県立医科大学, 医学部, 特任助教 (30635785)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血液凝固 / 新規治療 / インヒビター / 第VIII因子 / 出血性疾患 / FVIII / 血友病A / 血友病
Outline of Final Research Achievements

Hemophilia A (HA) is a severe bleeding disease caused by quantitative and/or qualitative defect of factor (F) VIII. The development of anti-FVIII alloantibodies (inhibitors) during the hemostatic treatment with FVIII concentrates, making the hemostatic effect unstable, is one of the most serious events for HA patients. In this study, we prepared the treatment model for HA with inhibitors in vitro and investigated the inhibitory mechanism(s) of the inhibitors as well as the hemostatic effect of the therapy. As results of the several experiments with the various assays, it was found that the differences in epitope(s) and inhibitory kinetics of inhibitors affected the neutralizing effect with high dose of FVIII and that the hemostatic effect of the bypassing agent was significantly enhanced by the presence of FVIII even with the inhibitor. These findings will make a basis for establishment of a novel hemostatic therapy for HA with inhibitors.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (10 results)

  • [Journal Article] The first case of int1h-related inversion in Japanese haemophilia A patients.2014

    • Author(s)
      Yada K, Nogami K, Kawamura T, Minami H, Shima M
    • Journal Title

      Haemophilia

      Volume: 20(6) Issue: 6

    • DOI

      10.1111/hae.12509

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 血友病に対する治療の進歩(1)-長時間作用型薬剤・抗体医薬の面から-2014

    • Author(s)
      矢田 弘史,野上 恵嗣
    • Journal Title

      臨床血液

      Volume: 55 Pages: 893-898

    • NAID

      130004688002

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different factor VIII neutralizing effects on anti-factor VIII inhibitor antibodies associated with epitope specificity and von Willebrand factor.2013

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

      British Journal of Haematology

      Volume: 163(1) Issue: 1 Pages: 104-111

    • DOI

      10.1111/bjh.12473

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activated prothrombin complex concentrate (APCC)-mediated activation of factor (F)VIII in mixtures of FVIII and APCC enhances hemostatic effectiveness.2013

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

      Journal of Thrombosis and Haemostasis

      Volume: 11(5) Issue: 5 Pages: 902-910

    • DOI

      10.1111/jth.12197

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The mild phenotype in severe hemophilia A with Arg1781His mutation is associated with enhanced binding affinity of factor VIII for factor X.2013

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

      Thrombosis and Haemostasis

      Volume: 109(6) Issue: 06 Pages: 1007-1015

    • DOI

      10.1160/th12-10-0762

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Activated protein C-catalyzed factor Va inactivation predominantly contributes to the downregulation of coagulation rather than factor VIIIa inactivation.2014

    • Author(s)
      Yada K, Nogami K, Matsumoto T, Kitazawa T, Hattori K, Shima M
    • Organizer
      56th ASH Annual meeting and Exposition
    • Place of Presentation
      米国(サンフランシスコ)
    • Year and Date
      2014-12-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Activated protein C-catalyzed factor Va inactivation is enhanced in the absence of factor VIIIa2014

    • Author(s)
      矢田 弘史,野上 恵嗣,松本 智子,北沢 剛久,服部 有宏,嶋 緑倫
    • Organizer
      第76回 日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] MC710はインヒビター存在下でも第VIII因子を直接活性化し,rFVIIaに比して相乗的に凝固機能を改善する2014

    • Author(s)
      矢田 弘史, 野上 恵嗣, 嶋 緑倫
    • Organizer
      第36回 日本血栓止血学会学術集会
    • Place of Presentation
      大阪国際交流センター
    • Year and Date
      2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 凝固一段法による第VIII因子活性(FVIII:C)が臨床的重症度を過小評価した軽症血友病Aの一例2013

    • Author(s)
      矢田弘史,野上 恵嗣, 荻原 建一, 松本 智子, 南 博明, 古川 晶子, 嶋 緑倫
    • Organizer
      第35回 日本血栓止血学会学術集会
    • Place of Presentation
      山形県
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel mechanism of development of the inhibitor distinguishing self from non-self associated with Pro1809Leu mutation.2013

    • Author(s)
      矢田弘史,野上恵嗣,武山 雅博,嶋 緑倫
    • Organizer
      第75回 日本血液学会学術集会
    • Place of Presentation
      北海道札幌市
    • Related Report
      2013 Research-status Report
  • [Presentation] Investigation of risk factors for hemophilic arthropathy in mild/moderate hemophilia A2013

    • Author(s)
      矢田弘史, 野上恵嗣, 嶋 緑倫
    • Organizer
      第55回 日本小児血液がん学会学術集会
    • Place of Presentation
      福岡県
    • Related Report
      2013 Research-status Report
  • [Presentation] Evaluation of the haemostatic potentials in a mild hemophilia A with a novel factor VIII mutation Thr677Ile2013

    • Author(s)
      Yada K , Nogami K, Ogiwara K and Midori Shima
    • Organizer
      XXIV ISTH Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Amsterdam,Netherlands
    • Related Report
      2013 Research-status Report
  • [Presentation] Different neutralizing effects of factor VIII concentrates associated with von willebrand factor and the inhibitor epitopes2013

    • Author(s)
      Yada K , Nogami K, Ogiwara K and Midori Shima
    • Organizer
      XXIV ISTH Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Amsterdam,Netherlands
    • Related Report
      2013 Research-status Report
  • [Presentation] Management of Bypassing Therapy in Hemophilia Patients with Inhibitors Utilizing Global Coagulation Assay.2013

    • Author(s)
      Yada K , Shima M
    • Organizer
      2013 East Asia Hemophilia Forum
    • Place of Presentation
      Seoul,Korea
    • Related Report
      2013 Research-status Report
  • [Presentation] Reduced affinity to VWF/PL induced by a novel mutation at P1809L (factor VIII-Tenri) is the cause of mild hemophilia A developing anti-factor VIII inhibitor2013

    • Author(s)
      Yada K, Nogami K , Takeyama M , Philip J. Fay and Shima M
    • Organizer
      55th ASH Annual meeting and Exposition
    • Place of Presentation
      New Orleans, U.S.A.
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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