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The development of appropriate diagnostic strategy for heparin-induced thrombocytopenia based on its unique immune response

Research Project

Project/Area Number 17K09912
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Miyata Shigeki  国立研究開発法人国立循環器病研究センター, 研究所, 客員研究員 (20239411)

Co-Investigator(Kenkyū-buntansha) 前田 琢磨  国立研究開発法人国立循環器病研究センター, 病院, 医長 (20713126)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsヘパリン起因性血小板減少症 / HIT抗体 / 血栓塞栓症 / HIT / 診断法 / 抗凝固 / 血栓 / 血栓止血 / 血液内科学 / 血小板
Outline of Final Research Achievements

Using a nationwide heparin-induced thrombocytopenia (HIT) registry, we analyzed data of 835 patients who were clinically suspected of having HIT. The results demonstrate that patients’ underlying diseases differentially impact HIT immune responses, especially the development of HIT antibodies with strong platelet-activating properties, and thus influence the timing of HIT onset, the incidence of HIT-associated thromboembolic event, and the timing of its onset. To investigate the uniqueness of HIT immune responses, we conducted a multicenter prospective observational study of trauma patients. As a result, seroconversion rates of HIT antibodies were higher as the severity of trauma increases. Moreover, severely injured patients developed HIT antibodies independent of heparin administration.
Considering clinical practices in Japan, we have established the evidence-based guidelines for the appropriate diagnosis and treatment of HIT.

Academic Significance and Societal Importance of the Research Achievements

ヘパリン起因性血小板減少症は、抗凝固薬であるヘパリン投与が、血小板活性化能を持つ抗体を誘導し、発症患者の約半数に、逆に血栓塞栓症を誘導する重篤な副反応である。希少疾病である本疾患について、全国規模でいくつかの臨床研究を実施することで、その理解困難な免疫応答の特異性を明らかにするとともに、本邦の臨床実態に配慮した、エビデンスに基づくHIT診断治療ガイドライン策定を行った。患者予後改善に資するものと考える。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (13 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results)

  • [Journal Article] HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) IN TRAUMA PATIENTS : SEVERE TISSUE DAMAGE AND INFLAMMATION CAN INDUCE HIT IMMUNE RESPONSES2020

    • Author(s)
      宮田 茂樹
    • Journal Title

      Journal of the Japanese Association for the Surgery of Trauma

      Volume: 34 Issue: 5 Pages: 137-148

    • DOI

      10.11382/jjast.34.5_01

    • NAID

      130007941675

    • ISSN
      1340-6264, 2188-0190
    • Year and Date
      2020-11-20
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extensive burns complicated with heparin-induced thrombocytopenia: A report of two cases2020

    • Author(s)
      Miyagawa Noriko、Fujita Motoo、Kawazoe Yu、Miyata Shigeki、Maeda Takuma、Kushimoto Shigeki
    • Journal Title

      Burns Open

      Volume: 4 Issue: 1 Pages: 37-40

    • DOI

      10.1016/j.burnso.2019.10.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful multi-step catheter intervention for thrombotic inferior vena cava filter retrieval2019

    • Author(s)
      Hayashi Hiroya、Tsuji Akihiro、Asano Ryotaro、Konagai Nao、Ueda Jin、Fukui Shigefumi、Ogo Takeshi、Miyata Shigeki、Yasuda Satoshi
    • Journal Title

      Journal of Cardiology Cases

      Volume: 20 Issue: 4 Pages: 142-146

    • DOI

      10.1016/j.jccase.2019.07.006

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 骨髄増殖性腫瘍患者の術後血栓予防における、ヘパリン起因性血小板減少症の1例2019

    • Author(s)
      新井康之、山中悠平、三好隆史、杉森英里、前田琢磨、宮田茂樹、山下浩平、高折晃史
    • Journal Title

      日本輸血細胞治療学会誌

      Volume: 65 Pages: 746-750

    • NAID

      130007709329

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Left ventricular assist device implantation after plasma exchange for heparin-induced thrombocytopenia2018

    • Author(s)
      Koizumi Shintaroh、Kohno Hiroki、Watanabe Michiko、Iwahana Togo、Maeda Takuma、Miyata Shigeki、Kobayashi Yoshio、Matsumiya Goro
    • Journal Title

      Journal of Artificial Organs

      Volume: 21 Issue: 4 Pages: 462-465

    • DOI

      10.1007/s10047-018-1055-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spinal anesthesia increases the risk of venous thromboembolism in total arthroplasty2017

    • Author(s)
      Nakamura Mashio、Kamei Masataka、Bito Seiji、Migita Kiyoshi、Miyata Shigeki、Kumagai Kenji、Abe Isao、Nakagawa Yasuaki、Nakayama Yuichiro、Saito Masanobu、Tanaka Takaaki、Motokawa Satoru
    • Journal Title

      Medicine

      Volume: 96 Issue: 18 Pages: e6748-e6748

    • DOI

      10.1097/md.0000000000006748

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ヘパリン起因性血小板減少症2017

    • Author(s)
      宮田茂樹
    • Journal Title

      日本臨牀

      Volume: 75 Pages: 291-296

    • NAID

      10031123859

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] HIT(ヘパリン起因性血小板減少症)2017

    • Author(s)
      宮田茂樹
    • Journal Title

      Coagulation & Inflammation

      Volume: 3 Pages: 3-11

    • NAID

      40021253472

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Underlying causes greatly influence the development of HIT antibodies and clinical outcomes in patients with heparin-induced thrombocytopenia2020

    • Author(s)
      Shigeki Miyata and Koichi Kokame
    • Organizer
      ISTH 2020: The XXVIII Congress of the International Society on Thrombosis and Haemostasis
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Association of platelet transfusion and its refractoriness with thromboembolic events in patients with heparin-induced thrombocytopenia2020

    • Author(s)
      Shigeki Miyata and Koichi Kokame
    • Organizer
      The 36th International ISBT (International Society of Blood Transfusion) congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Treatment strategy for patients suspected of having HIT in Japan2019

    • Author(s)
      Shigeki Miyata, Takuma Maeda
    • Organizer
      65th Annual Scientific and Standardization Committee (SSC) Meeting of International Society on Thrombosis and Haemostasis (ISTH)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Safety and efficacy of argatroban in Japanese patients with heparin-induced thrombocytopenia: a nationwide post-marketing surveillance study2019

    • Author(s)
      Shigeki Miyata, Okihiro Sawada, Yasuhiro Nakamura, Kaori Kuramochi
    • Organizer
      The 83rd Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2018 Research-status Report
  • [Presentation] 周術期大量出血、止血凝固異常に対する治療:迅速性を損なわない安全対策の検討2018

    • Author(s)
      宮田茂樹
    • Organizer
      第48回日本心臓血管外科学会学術総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] What are appropriate treatments for heparin-induced thrombocytopenia-associated thromboembolism?2018

    • Author(s)
      Shigeki Miyata
    • Organizer
      The 82nd Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ヘパリン起因性血小板減少症(HIT)患者への 血小板輸血が HIT 関連血栓症発症に与える 影響の検討2018

    • Author(s)
      宮田茂樹、前田琢磨
    • Organizer
      第40回日本血栓止血学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 機能的測定法で検出されるHIT抗体の血小板活性化能の強さと抗体陰性化までの期間の関係2017

    • Author(s)
      前田琢磨、光黒真菜、岡本 章、宮田茂樹
    • Organizer
      第39回日本血栓止血学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 重症外傷患者でヘパリン起因性血小板減少症を発症した場合,高率に血栓塞栓症を合併する2017

    • Author(s)
      宮田茂樹、岡本 章、光黒真菜、前田琢磨
    • Organizer
      第39回日本血栓止血学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Nationwide Heparin-Induced Thrombocytopenia(HIT) Registry: Towards Appropriate Diagnosis and Treatment of HIT in Japan2017

    • Author(s)
      Shigeki Miyata
    • Organizer
      XXVI ISTH Congress and 63rd Annual SSC Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Time to Disappearance of Platelet-activating Antibodies Depends on the Strength of Their Platelet Activating Properties in Patients with Heparin-induced Thrombocytopenia2017

    • Author(s)
      T. Maeda, H. Okazaki, S. Miyata
    • Organizer
      XXVI ISTH Congress and 63rd Annual SSC Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Impact of Platelet Transfusion on Thromboembolic Events in Patients with Acute Heparin-induced Thrombocytopenia2017

    • Author(s)
      S. Miyata, T. Maeda, H. Yamamoto, H. Okazaki,
    • Organizer
      XXVI ISTH Congress and 63rd Annual SSC Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヘパリン起因性血小板減少症(HIT)に合併する血栓塞栓症の特徴2017

    • Author(s)
      宮田茂樹
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-04-28   Modified: 2022-01-27  

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