Published online Jun 20, 2026. doi: 10.5662/wjm.v16.i2.113265
Revised: September 21, 2025
Accepted: December 30, 2025
Published online: June 20, 2026
Processing time: 246 Days and 11 Hours
Heparin-induced thrombocytopenia (HIT) is a severe immune adverse drug reac
To systematically compare the efficacy and safety of fondaparinux with that of argatroban and bivalirudin in patients who have been suspected or confirmed to have had HIT.
A systematic review of the literature has been conducted according to the PRISMA 2020 guidelines. Electronic databases were searched until January 2025. Randomized controlled trials (RCTs) and observational studies comparing the parenteral anticoagulant in patients with HIT were included. Study quality was assessed by two independent reviewers, based on the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for observational studies. Evidence certainty was conducted using the GRADE method.
The 2867 patients with HIT were identified in 16 of the studies that comprised this review (1 RCT, 15 RCTs). Limited head-to-head evidence was available from the single RCT. Across the studies, thrombotic events occurred at rates of 5%-15% and major bleeding at rates of 5%-15%. Research has shown differences in anticoagulation efficiency, with methodological differences being significant. Fondaparinux's safety characteristics were found favorable in retrospective reviews, whereas argatroban and bivalirudin displayed similar efficacy characteristics. The evidence certainty was classified as low to very low due to study design limitations and inconsistencies among key outcomes.
This systematic review identified significant gap in the comparative evidence to manage HIT using parenteral anticoagulants. Based on one RCT study and 15 observational studies (n = 2867), no single anticoagulant agent was definitively superior, and the certainty level of all outcomes was low to very low. Observational evidence and its methodological heterogeneity do not allow for ranking the treatment in an evidence-based treatment. Well-designed RCT are needed to guide in selecting the best anticoagulant to use in patients with HIT.
Core Tip: Heparin-induced thrombocytopenia is life-threatening and needs alternative anticoagulation. The systematic review included sixteen studies on 2867 patients treated with fondaparinux, bivalirudin and argatroban. None of these agents proved superior, and evidence certainty was low to very low, mainly because most studies were observational and showed heterogeneity. All three agents demonstrated acceptable efficacy and safety; however, treatment choice should be patient specific and clinically informed. Randomized trials are urgently needed to support evidence-based treatment decisions.