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

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09912
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: National 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
• Keywords: ヘパリン起因性血小板減少症 / HIT抗体 / 血栓塞栓症

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.

Free Research Field

血栓止血学、輸血学

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。