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Development of new examination methods for thrombotic tendency with TM resistance and FXa AT resistance

Research Project

Project/Area Number 25460683
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionNagoya University

Principal Investigator

TAKAGI AKIRA  名古屋大学, 医学(系)研究科(研究院), 准教授 (30135371)

Co-Investigator(Kenkyū-buntansha) KOJIMA Tetsuhito  名古屋大学, 大学院医学系研究科, 教授 (40161913)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords病態検査学 / 静脈血栓塞栓症 / 危険因子 / 病態解析 / プロトロンビン分子異常 / トロンボモジュリン抵抗性 / 血栓傾向
Outline of Final Research Achievements

Venous thromboembolism has attracted attention in recent years as economy class syndrome. In a congenital mutation of the blood coagulation factor control it has been known to increase the risk even in heterozygotes. We found an abnormal prothrombin to resist the control of the coagulation control factor antithrombin by one amino acid mutations, proposed an anti-thrombin resistance as a new disease concept. Thrombin loses the clotting ability to bind to receptor-thrombomodulin of vascular endothelial cell surface, so to exert an anti-clotting ability. We have developed a more of method for measuring changes in coagulation control ability of thrombomodulin by prothrombin mutation. In addition, we are focusing on the blood coagulation factor Xa inhibited by antithrombin.
We found abnormal FXs showing the antithrombin resistance. We have developed a method for analysis of FXa antithrombin resistance.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (29 results)

All 2016 2015 2014 2013

All Journal Article (8 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 3 results) Presentation (19 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] The first case of antithrombin-resistant prothrombin Belgrade mutation in Japanese2016

    • Author(s)
      Kishimoto M, Suzuki N, Murata M, Ogawa M, Kanematsu T, Takagi A, Kiyoi H, Kojima T, Matsushita T
    • Journal Title

      Ann Hematol.

      Volume: 95 Pages: 541-542

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 新たな血栓性素因:アンチトロンビンレジスタンス2016

    • Author(s)
      小嶋哲人、高木明、村田萌、高木夕希
    • Journal Title

      日本産婦人科・新生児血液学会誌

      Volume: 25 Pages: 66-72

    • Related Report
      2015 Annual Research Report
  • [Journal Article] アンチトロンビンレジスタンス ―新しい遺伝性血栓性素因―2015

    • Author(s)
      小嶋哲人、高木明、村田萌、高木夕希
    • Journal Title

      臨床血液

      Volume: 56 Pages: 632-637

    • NAID

      130005093096

    • Related Report
      2015 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Antithrombin- resistant prothrombin Yukuhashi mutation also causes thrombomodulin resistance in fibrinogen clotting but not in protein C activation.2014

    • Author(s)
      Takagi Y, Kato I, Ando Y, NakamuraY, Murata M, Takagi A, Murate T, Kojima T
    • Journal Title

      Thromb Res.

      Volume: 134 Issue: 4 Pages: 914-917

    • DOI

      10.1016/j.thromres.2014.07.040

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] A complex genomic abnormality found in a patient with antithrombin deficiency and autoimmune disease-like symptoms.2014

    • Author(s)
      Kato I, Takagi Y, Ando Y, Nakamura Y, Murata M, Takagi A, Murate T, Matsushita T, Nakashima T, Kojima T.
    • Journal Title

      Int J Hematol

      Volume: 100 Issue: 2 Pages: 200-205

    • DOI

      10.1007/s12185-014-1596-9

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] High prophylactic LMWH dose successfully suppressed hemostatic activation in pregnant woman with a new prpthrombin c.1787G>A mutation.2014

    • Author(s)
      Kovac M, Elezovic I, Mikovic V, Djordjevic V, Radojkovic D, Lalic-Cosic S, Murata M, Takagi A, Kojima T
    • Journal Title

      Thromb Res.

      Volume: 135 Issue: 2 Pages: 420-422

    • DOI

      10.1016/j.thromres.2014.12.008

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of new laboratory test to evaluate antithrombin resistance in plasma2014

    • Author(s)
      Murata M, Takagi A, Suzuki A, Okuyama E, Takagi Y, Ando Y, Kato I, Nakamura Y, Murate T, Matsushita T, Saito H, Kojima T.
    • Journal Title

      Thromb Res.

      Volume: 133 Pages: 293-299

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel prothrombin mutation in two families with prominent thrombophilia--the first cases of antithrombin resistance in a Caucasian population.2013

    • Author(s)
      Djordjevic V, Kovac M, Miljic P, Murata M, Takagi A, Pruner I, Francuski D, Kojima T, Radojkovic D.
    • Journal Title

      J Thromb Haemost

      Volume: 11 Issue: 10 Pages: 1936-1939

    • DOI

      10.1111/jth.12367

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Practical laboratory assay to detect abnormal prothrombin conveying thrombomodulin resistance2015

    • Author(s)
      高木夕希、水谷直貴、村田萌、小塚敏弘、中田悠紀子、長谷部瞭、河村奈美、槇山愛弓、橋本恵梨華、高木明、小嶋哲人高木夕希、水谷直貴、村田萌、小塚敏弘、中田悠紀子、長谷部瞭、河村奈美、槇山愛弓、橋本恵梨華、高木明、小嶋哲人
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] A congenital dysprothrombinemia with both decreased prothrombin activity and antithrombin resistance2015

    • Author(s)
      高田麻央、森下英里子、谷口文苗、關口暁子、小林英里奈、朝倉英策、高木明、小嶋哲人、大竹茂樹
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 深部静脈血栓症で発症したアンチトロンビンレジスタンス症例の抗凝固療法2015

    • Author(s)
      岸本磨由子、鈴木伸明、村田萌、小川実加、兼松毅、高木明、小嶋哲人、松下正
    • Organizer
      第16回日本検査血液検査血液学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-07-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 先天性アンチトロンビン欠乏症8症例SERPINC1遺伝子解析2015

    • Author(s)
      中田悠紀子、小塚敏弘、長谷部瞭、高木夕希、村田萌、上牧務、松尾真稔、高木明、松下正、小嶋哲人
    • Organizer
      第16回日本検査血液検査血液学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-07-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] アンチトロンビン抵抗性検出検査法の自動凝固検査機器への最適化 Part 22015

    • Author(s)
      村田萌、水谷直貴、高木夕希、長谷部瞭、小塚敏弘、中田悠紀子、高木明、松下正、小嶋哲人
    • Organizer
      第16回日本検査血液検査血液学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-07-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Analysis of prothrombin mutants in NA+ binding domain as a potential candidate conveying antithrombin resistance2015

    • Author(s)
      Moe Murata, Naoki Mizutani, Yuki Takagi, Ryo Hasebe, Toshihiro Kozuka, Yukiko Nakata, Akira Takagi, Tetsuhito Kojima
    • Organizer
      XXV Congress of International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2015-06-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] Analysis of prothrombin missense mutants at 596ARG by single nucleotide substitution for anticoagulant system2015

    • Author(s)
      Yuki Takagi, Moe Murata, Yuki Nakamura, Toshihiro Kozuka, Yukiko Nakata, Ryo Hasebe, Akira Takagi, Tetsuhito Kojima
    • Organizer
      XXV Congress of International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2015-06-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] ロトロンビン変異による新たなアンチトロンビン抵抗性変異の候補解析2015

    • Author(s)
      村田萌、水谷直貴、高木夕希、長谷部瞭、小塚敏弘、中田悠紀子、槇山愛弓、河村奈美、橋本恵梨華、高木明、松下正、小嶋哲人
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 深部静脈血栓症で発症しアンチトロンビン抵抗性を示した本邦初 Prothrombin Belgrade 変異の一家系2015

    • Author(s)
      岸本磨由子、鈴木伸明、村田萌、小川実加、兼松毅、高木明、小嶋哲人、松下正
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] プロトロンビンArg596 における一塩基置換ミスセンス変異体のトロンボモジュリン抵抗性評価2015

    • Author(s)
      高木夕希、村田萌、中村友紀、小塚敏弘、中田悠紀子、長谷部瞭、橋本恵梨華、高木明、小嶋哲人
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Optimization of the antithrombin resistance assay for the automated analyzer2014

    • Author(s)
      Moe Murata, Yuki Takagi, Yuki Nakamura, Ryo Hasebe, Toshihiro Kozuka, Yukiko Nakata, Akira Takagi, Tetsuhito Kojima
    • Organizer
      The 8th Congress of Asia Pacific Society of Thrombosis and Hemostasis
    • Place of Presentation
      Hanoi
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Precise genetic abnormalities in four hemophilia B patients with large deletions of X-chromosome including entire F82014

    • Author(s)
      Yuki Nakamura, Moe Murata, Yuki Takagi, Toshihiro Kozuka, Yukiko Nakata, Ryo Hasebe, Akira Takagi, Tadashi Matsushita, Tetsuhito Kojima
    • Organizer
      The 8th Congress of Asia Pacific Society of Thrombosis and Hemostasis
    • Place of Presentation
      Hanoi
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] アンチトロンビン抵抗性の関与が疑われた家族性再発性肺血栓塞栓症の1例2014

    • Author(s)
      吉田 律、角田 聖子、長谷川 潤、大木 理次、武本 知之、小山 達也、山崎 弘二、関 晋吾、吉村 道博、高木 明、小嶋 哲人
    • Organizer
      第233回日本循環器学会 関東・甲信越地方会
    • Place of Presentation
      東京
    • Year and Date
      2014-09-06
    • Related Report
      2014 Research-status Report
  • [Presentation] 原因不明であった静脈血栓塞栓症にみられたアンチトロンビン抵抗性を示す本邦2家系目のプロトロンビン異常症2014

    • Author(s)
      村田 萌、高木 明、岸本磨由子、清井 仁、松下 正、小嶋哲人
    • Organizer
      第33回日本臨床検査医学会東海・北陸支部例会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-08-02
    • Related Report
      2014 Research-status Report
  • [Presentation] アンチトロンビン抵抗性検出検査法の自動凝固検査機器への最適化2014

    • Author(s)
      村田 萌、高木夕希、中村友紀、長谷部 瞭、小塚敏弘、中田 悠紀子、高木 明、村手 隆、松下 正、小嶋哲人
    • Organizer
      第15回日本検査血液検査血液学会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2014-07-20 – 2014-07-21
    • Related Report
      2014 Research-status Report
  • [Presentation] A clinical laboratory test detecting antithrombin resistance of the new thrombophilia2013

    • Author(s)
      MURATA Moea, TAKAGI Akira, SUZUKI Atsuo,TAKAGI Yuki, KATO Io, ANDO Yumi, MURATE Takashi, MATSUSHITA Tadashi, SAITO Hidehiko, KOJIMA Tetsuhito
    • Organizer
      XXIV Congress of International Society on Thrombosis and Haemostasis,
    • Place of Presentation
      Amsterdam, The Neterlands
    • Related Report
      2013 Research-status Report
  • [Presentation] Effects of prothrombin Yukuhashi mutation on thrombomodulin-protein C system2013

    • Author(s)
      TAKAGI Yuki, KAT O Io, ANDO Yumi, MURATA Moea, SUZUKI Atsuo, TAKAGI Akira, MATSUSHITA Tadashi, SAITO Hidehiko, KOJIMA Tetsuhito
    • Organizer
      XXIV Congress of International Society on Thrombosis and Haemostasis,
    • Place of Presentation
      Amsterdam, The Neterlands
    • Related Report
      2013 Research-status Report
  • [Presentation] アンチトロンビン抵抗性解析法の改良と評価2013

    • Author(s)
      村田 萌、高木 明、中村友紀、加藤衣央、安藤裕実、高木夕希、村手 隆、松下 正、小嶋哲人
    • Organizer
      第14回日本検査血液検査血液学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] プロトロンビンYukuhashi由来変異型トロンビンのトロンボモジュリン・プロテインC系に及ぼす影響2013

    • Author(s)
      高木夕希、高木 明、鈴木敦夫、奥山恵理子、村田 萌、加藤衣央、安藤裕実、中村友紀、松下 正、齋藤英彦、小嶋哲人
    • Organizer
      第14回日本検査血液検査血液学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] 臨床検査法提要(改訂第34版)2015

    • Author(s)
      小嶋哲人、高木明
    • Total Pages
      21
    • Publisher
      金原出版株式会社
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 血栓症のリスク検査法2013

    • Inventor(s)
      高木明、小嶋哲人、高木夕希、村田萌
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-07-17
    • Related Report
      2013 Research-status Report

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

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