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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 21591370
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
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) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords血液凝固 / 第VIII因子 / 外因系 / 線溶系 / 凝固抑制系 / 酵素 / 相互作用 / 活性化/不活化 / 活性型第VII因子 / 長時間作用型 / 炎症性因子 / 結合部位 / プラスミン / インヒビター / 活性化 / 不活化 / プロテインS
Research Abstract

Factor VIII(FVIII) is an extremely important blood coagulation factor in the opposite conditions such as the hemorrhages and thrombi. However, there are still uncertain points on FVIII-based(anti-) coagulation and thrombus formation. The conventional researches of blood coagulation had been fully done separately by the intrinsic and extrinsic pathway, anti-coagulant pathway, and fibrinolytic pathway, but it is being now supported that all pathways simultaneously participate and progress in coagulation. In this study, we for the first time found the relationship of FVIII with plasmin(fibrinolytic factor), FVIIa(extrinsic factor), protein S(anti-coagulant factor), neutrophil elastase(inflammatory factor) during the blood coagulation process.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (69 results)

All 2011 2010 2009

All Journal Article (25 results) (of which Peer Reviewed: 13 results) Presentation (35 results) Book (9 results)

  • [Journal Article] Interactions between residues 2228-2240 within factor VIIIa C2 domain and factor IXa Gla domain contribute to propagation of clot formation2011

    • Author(s)
      Soeda T, Nogami K, 他2名
    • Journal Title

      Thromb Haemost

      Volume: 106 Pages: 893-900

    • Related Report
      2011 Final Research Report
  • [Journal Article] Factor VIII activation by factor VIIa analog(V158D/E296V/M298Q) in tissue factor independent mechanisms2011

    • Author(s)
      Ogiwara K, Nogami K, 他1名
    • Journal Title

      Thromb Haemost

      Volume: 106 Pages: 665-74

    • Related Report
      2011 Final Research Report
  • [Journal Article] Mechanisms of human neutrophil elastase-catalysed inactivation of factor VIII(a)2011

    • Author(s)
      Nogami K, Ogiwara K, 他4名
    • Journal Title

      Thromb Haemost

      Volume: 105 Pages: 968-80

    • Related Report
      2011 Final Research Report
  • [Journal Article] Effects of anti-factor VIII inhibitor antibodies on factor VIIa/tissue factor-catalysed activation and inactivation of factor VIII2011

    • Author(s)
      Yada K, Nogami K, 他3名
    • Journal Title

      Thromb Haemost

      Volume: 105 Pages: 989-98

    • Related Report
      2011 Final Research Report
  • [Journal Article] Mechanisms of human neutrophil elastase-catalysed inactivation of factor VIII(a)2011

    • Author(s)
      Nogami K, Ogiwara K, et al
    • Journal Title

      Thrombosis and Haemostasis

      Volume: 105 Pages: 968-980

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interactions between residues 2228-2240 within factor VIIIa C2 domain and factor IXa Gla domain contribute to propagation of clot formation2011

    • Author(s)
      Soeda T, Nogami K,(corresponding author), et al
    • Journal Title

      Thrombosis and Haemostasis

      Volume: 106 Pages: 893-900

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Factor VIII activation by factor VIIa analog (V158D/E296V/M298Q) in tissue factor-independent mechanisms2011

    • Author(s)
      Ogiwara K, Nogami K (corresponding author), et al
    • Journal Title

      Thrombosis and Haemostasis

      Volume: 106 Pages: 665-674

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of anti-factor VIII inhibitor antibodies on factor VIIa/tissue factor-catalysed activation and inactivation of factor VIII2011

    • Author(s)
      Yada K, Nogami K (corresponding author), et al
    • Journal Title

      Thrombosis and Haemostasis

      Volume: 105 Pages: 989-998

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of anti-factor VIII inhibitor antibodies on factor VIIa/tissue factor-catalyzed activation and inactivation of factor VIII2011

    • Author(s)
      Yada K, Nogami K (corresponding author), et al.
    • Journal Title

      Thrombosis and Haemostasis

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of factor VIIa-catalyzed activation of factor VIII2010

    • Author(s)
      Soeda T, Nogami K, 他3名
    • Journal Title

      J Thromb Haemost

      Volume: 8 Pages: 2494-503

    • Related Report
      2011 Final Research Report
  • [Journal Article] Plasmin induced procoagulant effects in the blood coagulation : a crucial role of coagulation factors V and VIII2010

    • Author(s)
      Ogiwara K, Nogami K, 他2名
    • Journal Title

      Blood Coagul Fibrinolysis

      Volume: 21 Pages: 568-76

    • Related Report
      2011 Final Research Report
  • [Journal Article] Determination of a factor VIII interactive region within plasmin responsible for plasmin-catalysed activation and inactivation of factor VIII(a)2010

    • Author(s)
      Nishiya K, Nogami K, 他5名
    • Journal Title

      Thromb Haemost

      Volume: 104 Pages: 105-17

    • Related Report
      2011 Final Research Report
  • [Journal Article] Characterisation of an antibody specific for coagulation factor VIII that enhances factor VIII activity2010

    • Author(s)
      Takeyama M, Nogami K, 他5名
    • Journal Title

      Thromb Haemost

      Volume: 103 Pages: 94-102

    • Related Report
      2011 Final Research Report
  • [Journal Article] Mechanisms of factor VIIa-catalyzed activation of factor VIII2010

    • Author(s)
      Soeda T, Nogami K (correspondingauthor), et al.
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 8 Pages: 2494-2503

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasmin-induced procoagulant effects in the blood coagulation : a crucial role of coagulation factors V and VIII2010

    • Author(s)
      Ogiwara K, Nogami K (corresponding author), et al.
    • Journal Title

      Blood Coagulation and Fibrinolysis

      Volume: 21 Pages: 768-776

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determination of a factor VIII-interactive region within plasmin responsible for plasmin-catalysed activation and inactivation of factor VIII(a)2010

    • Author(s)
      Nishiya K, Nogami K (corresponding author), et al.
    • Journal Title

      Thrombosis and Haemostasis

      Volume: 104 Pages: 105-117

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determination of a factor VIII-interactive region within plasmin responsible for plasmin-catalyzed activation and inactivation of factor VIII(a)2010

    • Author(s)
      Nishiya K, Nogami K(corresponding author), et al.
    • Journal Title

      Thrombosis and Haemostasis (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of an antibody specific for coagulation factor VIII that enhances factor VIII(a)activity2010

    • Author(s)
      Takeyama M, Nogami K(corresponding author), et al.
    • Journal Title

      Thrombosis and Haemostasis 103

      Pages: 94-102

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a protein S interactive site within the A2 domain of the factor VIII heavy chain2009

    • Author(s)
      Takeyama M, Nogami K, 他3名
    • Journal Title

      Thromb Haemost

      Volume: 102 Pages: 645-55

    • Related Report
      2011 Final Research Report
  • [Journal Article] Identification of plasmin-interactive sites in the light chain of factor VIII responsible for proteolytic cleavage at Lys362009

    • Author(s)
      Nogami K, 他6名
    • Journal Title

      J Biol Chem

      Volume: 284 Pages: 6934-45

    • Related Report
      2011 Final Research Report
  • [Journal Article] The factor VIIIa C2 domain(residues 2228-2240) interacts with the factor IXa Gla domain in the factor Xase complex2009

    • Author(s)
      Soeda T, Nogami K, 他6名
    • Journal Title

      J Biol Chem

      Volume: 284 Pages: 3379-88

    • Related Report
      2011 Final Research Report
  • [Journal Article] A modified thrombin generation test for investigating very low levels of factor VIII activity in hemophilia A2009

    • Author(s)
      Matsumoto T, Nogami K, 他2名
    • Journal Title

      Int J Hematol

      Volume: 90 Pages: 576-82

    • NAID

      10026109911

    • Related Report
      2011 Final Research Report
  • [Journal Article] Identification of a protein S-interactive site within the A2 domain of the factor VIII heavy chain2009

    • Author(s)
      Takeyama M, Nogami K(corresponding author), et al.
    • Journal Title

      Thrombosis and Haemostasis 102

      Pages: 645-655

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] von Willebrand factor protects the Ca2+-dependent structure of the factor VIII light chain2009

    • Author(s)
      Takeyama M, Nogami K(corresponding author), et al.
    • Journal Title

      British Journal of Haemotology 146

      Pages: 531-536

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A modified thrombin generation test for investigating very low levels of factor VIII activity in hemophilia A2009

    • Author(s)
      Matsumoto T, Nogami K(corresponding author), et al.
    • Journal Title

      International Journal of Haemotology 90

      Pages: 576-582

    • NAID

      10026109911

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] A novel mechanism of enhancing the haemostatic effect in the combination with recombinant factor VIII and activated prothrombin complex concentrate (APCC) in hemophilia A patients with Inhibitor2011

    • Author(s)
      Yada K, Nogami K (corresponding author), et al
    • Organizer
      第53回annual meeting of American Society of Hematology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2011-12-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effects of anti-FVIII inhibitors on the FVIII neutralization therapy for hemophilia A with inhibitor2011

    • Author(s)
      矢田弘史、野上恵嗣(corresponding author), et al
    • Organizer
      第73回日本血液学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-10-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Procoagulant effect of tranexamic acid with minimal urokinase on ex vivo human hemophilia model under blood flow2011

    • Author(s)
      Ogiwara K, Nogami K (corresponding author), et al
    • Organizer
      第23回International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2011-07-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Mild clinical phenotype in a severe hemophilia A with Arg1781Hissubstitution associated with increased factor Xa generation2011

    • Author(s)
      Yada K, Nogami K (corresponding author), et al
    • Organizer
      第23回International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2011-07-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] A role and mechanism of plasmin-catalyzed factor VIII activation in blood coagulation and fibrinolysis2011

    • Author(s)
      Nogami K
    • Organizer
      第23回International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2011-07-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] A role and mechanism of plasmin catalyzed factor VIII activation in blood coagulation and fibrinolysis2011

    • Author(s)
      Nogami K
    • Organizer
      第23回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Mechanism of the potent activated protein C resistance of novel factor V mutation with W1920R(FV Nara) relative to R506Q(FV Leiden)2011

    • Author(s)
      Ogiwara K, Nogami K, et al
    • Organizer
      第53回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] A novel mechanism of enhancing the haemostatic effect in the combination with recombinant factor VIII and activated prothrombin complex concentrate(APCC) in hemophilia A patients with Inhibitor2011

    • Author(s)
      Yada K, Nogami K, et al
    • Organizer
      第53回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Evaluation of comprehensive hemostatic function of patients with von Willebrand disease(VWD) under flow using a new microchip flow chamber system2011

    • Author(s)
      Ogiwara K, Nogami K, et al
    • Organizer
      第53回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Pharmacokinetics of continuous infusion therapy of factor VIII concentrates in hemophilia A patients with inhibitors2011

    • Author(s)
      Nishiya K, Tanaka I, Nogami K, et al
    • Organizer
      第53回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Coagulation velocity and acceleration correlate with clinical phenotype of patients with acquired factor V inhibitors2011

    • Author(s)
      Matsumoto T, Nogami K, et al
    • Organizer
      第23回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Perioperative hemostatic management for coarctation of aorta in an early infant with severe haemophilia A2011

    • Author(s)
      Furukawa S, Yoshizawa H, Ogiwara K, Nogami K, et al
    • Organizer
      第23回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Procoagulant effect of tranexamic acid with minimal urokinase on ex vivo human hemophilia model under blood flow2011

    • Author(s)
      Ogiwara K, Nogami K, et al
    • Organizer
      第23回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Mild clinical phenotype in a severe hemophilia A with Arg1781His substitution associated with increased factor Xa generation2011

    • Author(s)
      Yada K, Nogami K, et al
    • Organizer
      第23回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] A novel missense mutation of factor V(factor V Nara : W1920R) manifested thrombosis and demonstrated a positive result of activated protein C resistance assay2011

    • Author(s)
      Shinozawa K, Nogami K, et al
    • Organizer
      第23回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Dynamics of plasma factor VIII during the continuous infusion of factor VIII concentrates in twenty patients with hemophilia A2011

    • Author(s)
      Nishiya K, Nogami K, et al
    • Organizer
      第23回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Procoagulant activity of antifibrinolytic agents : A novel hemostatic mechanism of tranexamic and epsilon-aminocaproic acid2010

    • Author(s)
      Ogiwara K, Nogami K (corresponding author), et al.
    • Organizer
      第52回米国血液学会発表
    • Place of Presentation
      Orland, FL, USA
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] Tissue factor pathway inhibitor causes unresponsiveness to activated prothrombin complex concentrates for hemophilia A patients with inhibitor2010

    • Author(s)
      Ogiwara K, Nogami K (corresponding author), et al.
    • Organizer
      第52回米国血液学会発表
    • Place of Presentation
      Orland, FL, USA
    • Year and Date
      2010-12-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] Determination of coagulation functions and inhibitory mechanisms in acquired hemophilia A with type 1 and type 2 inhibitors2010

    • Author(s)
      Matsumoto T, Nogami K (corresponding author), et al.
    • Organizer
      第52回米国血液学会発表
    • Place of Presentation
      Orland, FL, USA
    • Year and Date
      2010-12-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] Tissue factor pathway inhibitor causes unresponsiveness to activated prothrombin complex concentrates for hemophilia A patients with inhibitors2010

    • Author(s)
      Ogiwara K, Nogami K, et al
    • Organizer
      第52回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Determination of coagulation functions and inhibitory mechanisms in acquired hemophilia A with type 1 and type 2 inhibitors2010

    • Author(s)
      Matsumoto T, Nogami K, et al
    • Organizer
      第52回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Procoagulant activity of antifibrinolytic agents ; A novel hemostatic mechanism of tranexamic acid and epsilon-aminocaproic acid2010

    • Author(s)
      Ogiwara K, Nogami K, et al
    • Organizer
      第52回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Dynamics of plasma factor VIII during the continuous infusion of factor VIII concentrates in patients with hemophilia A2010

    • Author(s)
      Nishiya K, Tanaka I, Nogami K, et al
    • Organizer
      East Asia Haemophilia Forum
    • Related Report
      2011 Final Research Report
  • [Presentation] Interactions of factor VIII with tissue factor contributes to the acceleration of factor Xa generation in the initiation phase of blood coagulation2009

    • Author(s)
      Ogiwara K, Nogami K(corresponding author), et al.
    • Organizer
      第51回米国血液学会発表
    • Place of Presentation
      New Orleans, LA, USA
    • Year and Date
      2009-12-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] Effects of anti-FVIII inhibitors on factor VIIa/tissue factor-catalyzed activation and inactivation of factor VIII2009

    • Author(s)
      Yada K, Nogami K(corresponding author), et al.
    • Organizer
      第51回米国血液学会発表
    • Place of Presentation
      New Orleans, LA, USA
    • Year and Date
      2009-12-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] Mechanisms of human neutrophil elastase-catalyzed inactivation of the factor VIII(a)2009

    • Author(s)
      Nishiya K, Nogami K(corresponding author), et al.
    • Organizer
      第51回米国血液学会発表
    • Place of Presentation
      New Orleans, LA, USA
    • Year and Date
      2009-12-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Elevation of coagulant activity by plasmin via factor VIII on the blood coagulation2009

    • Author(s)
      Ogiwara K, Nogami K(corresponding author), et al.
    • Organizer
      第22回国際血栓止血学会
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2009-07-15
    • Related Report
      2009 Annual Research Report
  • [Presentation] Determination for coagulation functions and novel inhibitory mechanisms in acquired hemophilia A with type 2 inhibitors2009

    • Author(s)
      Matsumoto T, Nogami K, et al
    • Organizer
      第51回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Effects of anti-FVIII inhibitors on factor VIIa tissue factor-catalyzed activation and inactivation of factor VIII2009

    • Author(s)
      Yada K, Nogami K, et al
    • Organizer
      第51回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Interactions of factor VIII with tissue factor contributes to the acceleration of factor Xa generation in the initiation phase of blood coagulation2009

    • Author(s)
      Ogiwara K, Nogami K, et al
    • Organizer
      第51回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Mechanisms of human neutrophil elastase-catalyzed inactivation of the factor VIII(a)2009

    • Author(s)
      Nishiya K, Nogami K, et al
    • Organizer
      第51回米国血液学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Mechanisms of factor VIII activation by factor VIIa and its analog NN1731(V158D/E296V/M298Q)2009

    • Author(s)
      Ogiwara K, Nogami K, et al
    • Organizer
      第10回Novo Nordisk Symposium on Hemostasis Management
    • Related Report
      2011 Final Research Report
  • [Presentation] Deep venous thromboembolism in a patient of factor V deficiency2009

    • Author(s)
      Nishiya K, Nogami K, et al
    • Organizer
      第22回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Anti-A2 monoclonal antibody enhancing thrombin and factor Xa-catalyzed factor VIII activity2009

    • Author(s)
      Takeyama M, Nogami K, et al
    • Organizer
      第22回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Presentation] Procoagulant effect of plasmin dependent on factor V and factor VIII during the blood coagulation process2009

    • Author(s)
      Ogiwara K, Nogami K, et al
    • Organizer
      第22回国際血栓止血学会
    • Related Report
      2011 Final Research Report
  • [Book] 血栓と循環「血栓症に関するQ&A」2011

    • Author(s)
      野上恵嗣
    • Publisher
      メディカルレビュー社
    • Related Report
      2011 Annual Research Report
  • [Book] 「小児の診療のしかた-あなたの疑問に答えます」出血傾向を認める患児のスクリーニング検査は何を行いますか?2011

    • Author(s)
      野上恵嗣
    • Publisher
      小児内科
    • Related Report
      2011 Annual Research Report
  • [Book] 血栓と循環「血液凝固反応の内因系と外因系は、現在どのように考えられているのですか?」2011

    • Author(s)
      野上恵嗣
    • Total Pages
      2
    • Publisher
      メディカルレビュ社
    • Related Report
      2010 Annual Research Report
  • [Book] 小児科診療ガイド「von Willebrand病」2011

    • Author(s)
      野上恵嗣、嶋緑倫
    • Total Pages
      4
    • Publisher
      中山書店
    • Related Report
      2010 Annual Research Report
  • [Book] Clinical and Laboratory Examination in Hemophilia Sysmex2010

    • Author(s)
      Nogami Keiji, Shima Midori
    • Publisher
      シスメックス
    • Related Report
      2011 Final Research Report
  • [Book] 血液疾患血液凝固異常小児科学レビュー2010

    • Author(s)
      野上恵嗣, 嶋緑倫
    • Total Pages
      111
    • Publisher
      総合医学社
    • Related Report
      2011 Final Research Report
  • [Book] 血友病に対する適切な治療.臨床に直結する血液疾患診療のエビデンス2009

    • Author(s)
      野上恵嗣, 嶋緑倫
    • Publisher
      文光堂
    • Related Report
      2011 Final Research Report
  • [Book] 血友病A-第VIII因子の分子生物学的診断の進歩. Annual Review 2009血液2009

    • Author(s)
      野上恵嗣
    • Publisher
      中外医学社
    • Related Report
      2011 Final Research Report
  • [Book] 小児疾患診療のための病態生理2血友病.小児内科2009

    • Author(s)
      野上恵嗣, 嶋緑倫
    • Total Pages
      1124
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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