Comparative effectiveness and safety of anticoagulants for the treatment of heparin-induced thrombocytopenia

Am J Hematol. 2021 Jul 1;96(7):805-815. doi: 10.1002/ajh.26194. Epub 2021 May 3.


Background: The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability.

Methods: Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random-effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed.

Results: Out of 3194 articles screened, 92 studies with 119 treatment groups describing 4698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article.

Discussion: Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Blood Platelets / drug effects
  • Hemorrhage / chemically induced
  • Heparin / adverse effects*
  • Heparin / therapeutic use
  • Humans
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / drug therapy
  • Thromboembolism / drug therapy
  • Treatment Outcome


  • Anticoagulants
  • Heparin