Comparative effectiveness of parenteral anticoagulants (fondaparinux, argatroban, bivalirudin) in heparin-induced thrombocytopenia: A systematic review.

Abstract

Background: Heparin-induced thrombocytopenia (HIT) is a severe immune adverse drug reaction that requires stopping heparin and starting other types of anticoagulation. The comparative effectiveness of intravenous anticoagulants remains uncertain.

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.