Association of trauma severity with antibody seroconversion in heparin-induced thrombocytopenia: A multicenter, prospective, observational study

Motoo Fujita, Takuma Maeda, Shigeki Miyata, Asumi Mizugaki, Mineji Hayakawa, Noriko Miyagawa, Noritaka Ushio, Atsushi Shiraishi, Takayuki Ogura, Shiho Irino, Kazuhiko Sekine, Yoshihisa Fujinami, Kazutaka Kiridume, Toru Hifumi, Shigeki Kushimoto

Research output: Contribution to journalArticlepeer-review


BACKGROUND Heparin administration can induce the production of anti-platelet factor 4 (PF4)/heparin antibodies with platelet-activating properties, causing heparin-induced thrombocytopenia (HIT). Previous studies have suggested that trauma severity influences HIT immune responses, but their relationship has not been fully explained. This study aimed to clarify this association by multicenter prospective observational study. METHODS Trauma patients who met the criteria of age 18 years or older and Injury Severity Scores (ISSs) of ≥9 from March 2018 to February 2019 were included. Patients who did not receive any heparin and those who received it as flushes or for treatment were also included. Patients were divided into three groups based on trauma severity (to mild [ISS 9-15], moderate [ISS 16-24], and severe injury groups [ISS ≥25]) and were compared by the seroconversion time and rate, as well as the disappearance rate of antibodies on day 30. RESULTS A total of 184 patients were included: 55, 62, and 67 patients were classified into the mild, moderate, and severe injury groups, respectively. Overall, the seroconversion rates of anti-PF4/heparin immunoglobulin G (IgG) and HIT antibodies by washed platelet activation assay were 26.6% and 16.3%, respectively. There was a significant difference in the seroconversion rates of anti-PF4/heparin IgG (p = 0.016) and HIT antibodies (p = 0.046) among the groups. Seroconversion rates in both assays increased with increasing trauma severity. The time required to achieve seroconversion was similar (between 5 and 10 days of trauma onset) regardless of heparin administration. Anti-PF4/heparin IgG and HIT antibodies were no longer detected on day 30 in 28.6% and 60.9% of seroconverted patients, respectively. CONCLUSION Development of HIT antibodies was observed commonly in severely injured trauma patients. Heparin-induced thrombocytopenia antibody development may be related to trauma severity, with a high disappearance frequency on day 30. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III.

Original languageEnglish
Pages (from-to)402-408
Number of pages7
JournalJournal of Trauma and Acute Care Surgery
Issue number3
Publication statusPublished - 2022 Sept 1


  • Critically ill
  • heparin-induced thrombocytopenia
  • seroconversion
  • thrombosis

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine


Dive into the research topics of 'Association of trauma severity with antibody seroconversion in heparin-induced thrombocytopenia: A multicenter, prospective, observational study'. Together they form a unique fingerprint.

Cite this