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Development of monitoring tests for residual coagulation activity in novel oral anticoagulants

Research Project

Project/Area Number 15K08621
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

Ieko Masahiro  北海道医療大学, 歯学部, 教授 (50250436)

Co-Investigator(Kenkyū-buntansha) 高橋 伸彦  北海道医療大学, 歯学部, 准教授 (20372279)
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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords抗凝固療法 / 新規経口抗凝固薬 / 血栓症 / 直接経口Xa阻害薬 / 血栓塞栓症 / 直接経口抗凝固薬 / エカリン / 希釈プロトロンビン時間 / 血栓マーカー / ダビガトラン / 直接Xa阻害薬
Outline of Final Research Achievements

Novel oral anticoagulants (NOAC) are considered unnecessary for monitoring tests, however the test that can indicate the excess and under-dosage of NOAC is necessary for effective anticoagulant therapy.
We developed Thrombin Inhibition Ratio (TIR) using Ecarin Clotting Time for dabigatran therapy. TIR correlated well with the blood dabigatran concentration (r2 = 0.66). Then, for direct oral factor Xa inhibitors (Xa-INH) therapy, we developed Ratio of inhibited thrombin generation (RITG) using dilute PT. RITG correlated with the blood concentration of each Xa-INH (Rivaroxaban: r2 = 0.51, Apixaban: 0.45, Edoxaban: 0.75). In samples with low value of TIR or RITG, there were many samples with increased thrombus markers such as FMC. TIR and RITG can reflect the excess and under-dosage of NOAC. Also, RITG is a unique test that can simultaneously evaluate the effects of three kinds of Xa-INH. We are planning to consider more effective NOAC therapy using these indexes in the future.

Report

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

    (21 results)

All 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Differences in coagulofibrinolytic changes between post-cardiac arrest syndrome of cardiac causes and hypoxic insults: a pilot study.2017

    • Author(s)
      Wada T, Gando S, Mizugaki A, Kodate A, Sadamoto Y, Murakami H, Maekawa K, Katabami K, Ono Y, Hayakawa M, Sawamura A, Jesmin S, Ieko M.
    • Journal Title

      Acute Med Surg.

      Volume: 27;4(3) Issue: 3 Pages: 371-372

    • DOI

      10.1002/ams2.270

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sarcolipin expression is repressed by endoplasmic reticulum stress in C2C12 myotubes2017

    • Author(s)
      Takahashi Nobuhiko、Kimura Atsushi P.、Naito Sumiyoshi、Yoshida Mika、Kumano Osamu、Suzuki Takeshi、Itaya Satoshi、Moriya Mitsuru、Tsuji Masahiro、Ieko Masahiro
    • Journal Title

      Journal of Physiology and Biochemistry

      Volume: 73 Issue: 4 Pages: 531-538

    • DOI

      10.1007/s13105-017-0578-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics and outcomes of acquired hemophilia A: experience at a single center in Japan2017

    • Author(s)
      Ogawa Yoshiyuki、Yanagisawa Kunio、Uchiumi Hideki、Ishizaki Takuma、Mitsui Takeki、Gouda Fumito、Ieko Masahiro、Ichinose Akitada、Nojima Yoshihisa、Handa Hiroshi
    • Journal Title

      Int J Hematol

      Volume: 106 Issue: 1 Pages: 82-89

    • DOI

      10.1007/s12185-017-2210-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid remission of severe pain from livedoid vasculopathy by apixaban.2016

    • Author(s)
      Yamaguchi Y, Nakazato S, Izumi K, Ieko M, Nomura T, Shimizu H.
    • Journal Title

      J Eur Acad Dermatol Venereol

      Volume: 印刷中 Issue: 1

    • DOI

      10.1111/jdv.13691

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Profiles of direct oral anticoagulants and clinical usage-dosage and dose regimen differences.2016

    • Author(s)
      Ieko M, Naitoh S, Yoshida M, Takahashi N.
    • Journal Title

      J Intensive Care.

      Volume: 10 Issue: 1 Pages: 4-19

    • DOI

      10.1186/s40560-016-0144-5

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel oral anticoagulants (NOAC)2015

    • Author(s)
      家子正裕
    • Journal Title

      Rinsho Ketsueki

      Volume: 56 Issue: 10 Pages: 2123-2133

    • DOI

      10.11406/rinketsu.56.2123

    • NAID

      130005103288

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2015 Research-status Report
    • Open Access
  • [Presentation] 直接経口抗凝固薬(DOAC)のモニタリング検査と拮抗薬.2017

    • Author(s)
      家子正裕
    • Organizer
      第44回日本集中治療医学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] DOACのモニタリングと中和剤について2017

    • Author(s)
      家子正裕
    • Organizer
      第39回日本血栓止血学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 経口直接Xa阻害薬療法おける抗凝固効果の確認に関する検討2017

    • Author(s)
      1.鈴木健史, 家子正裕, 高橋伸彦,内藤澄悦,吉田美香,熊野穣,畑中大希,末武司,小宮山豊,佐久間一郎
    • Organizer
      第18回日本検査血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Fibrin Monomer complex and diluted prothrombin time as a marker for thrombotic tendency in anti-Xa DOAC therapy.2017

    • Author(s)
      Suzuki T, Ieko M, Naito S, Yoshida M, Komiyama Y, Hatanaka D, Kumano O, Suetake T, Takahashi N, Sakuma I
    • Organizer
      The 26th International Society on Thrombosis and Haemostasis Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] New evaluation test for direct oral factor Xa inhibitors using diluted prothrombin time2017

    • Author(s)
      Naito S, Ieko M, Suzuki T, Yoshida M, Omura K, Takahashi N, Moriya M, Wakamiya N, Sakuma I
    • Organizer
      The 29th World Congress of World Association of Societies of Pathology and Laboratory Medicine
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 直接経口抗凝固薬の抗凝固効果から有用性と限界を探る2016

    • Author(s)
      家子正裕、内藤済悦、吉田美香、高橋伸彦
    • Organizer
      第37回日本臨床薬理学会
    • Place of Presentation
      米子市
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 経口Xa阻害薬における抗凝固効果の新たな確認試験2016

    • Author(s)
      内藤済悦、家子正裕、佐久間一郎、鈴木健史、熊野穣、吉田美香、高橋伸彦、四倉昭彦、ほか
    • Organizer
      第36回日本臨床検査医学会
    • Place of Presentation
      神戸市
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] エドキサバン療法における希釈プロトロンビン時間を用いた残存凝固能(RITG)の測定2016

    • Author(s)
      内藤済悦、家子正裕、佐久間一郎、鈴木健史、熊野穣、吉田美香、高橋伸彦、四倉昭彦、ほか
    • Organizer
      第38回日本血栓止血学会
    • Place of Presentation
      奈良市
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Edoxaban服用者における血栓マーカーを用いたRatio of Inhibited Thrombin Generationの評価2016

    • Author(s)
      鈴木健史、家子正裕、佐久間一郎、熊野穣、内藤済悦、吉田美香、高橋伸彦、四倉昭彦、ほか
    • Organizer
      第38回日本血栓止血学会
    • Place of Presentation
      奈良市
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 直接経口抗凝固薬服用患者のプロトロンビン時間と活性化部分トロンボプラスチン時間の日差変動2016

    • Author(s)
      山崎昌子、志賀剛、長尾毅彦、遠井素乃、水野聡子、家子正裕、北川一夫
    • Organizer
      第38回日本血栓止血学会
    • Place of Presentation
      奈良市
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 各種Direct Oral Anticoagulants服用中の血中濃度の比較2015

    • Author(s)
      鈴木健史、家子正裕、佐久間一郎、他
    • Organizer
      第62回日本臨床検査医学会
    • Place of Presentation
      岐阜市
    • Year and Date
      2015-11-19
    • Related Report
      2015 Research-status Report
  • [Presentation] 新規経口抗凝固薬2015

    • Author(s)
      家子正裕
    • Organizer
      第77回日本血液学会
    • Place of Presentation
      金沢市
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 新規経口抗凝固薬(NOAC)の服用が日常凝固時間検査に及ぼす影響2015

    • Author(s)
      内藤済悦、家子正裕、佐久間一郎、他
    • Organizer
      第16回日本検査血液学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-07-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Evaluation of anticoagulant therapy with Dabigatran based on ecarin clotting time2015

    • Author(s)
      K. Suzuki, M. Ieko, I. Sakuma, et al
    • Organizer
      XXV Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      Toronto
    • Year and Date
      2015-06-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 各種NOAC服用者における血栓マーカーの比較2015

    • Author(s)
      鈴木健史、家子正裕、佐久間一郎、他
    • Organizer
      第37回日本血栓止血学会
    • Place of Presentation
      甲府市
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report

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

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