Fondaparinux versus argatroban for the management of suspected or confirmed heparin-induced thrombocytopenia: a propensity score-matched cohort study.

Background: Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse drug reaction associated with significant morbidity and mortality. While argatroban is guideline-recommended, fondaparinux is increasingly used off-label; however, comparative real-world data remain limited, particularly in critically ill populations. Objective: To compare the effectiveness and safety of fondaparinux versus argatroban in patients with suspected or confirmed HIT. Methods: This retrospective cohort study included adult patients treated with fondaparinux or argatroban for suspected or confirmed HIT. Argatroban was administered as a continuous intravenous infusion with activated partial thromboplastin time (aPTT)-guided titration, whereas fondaparinux was given as fixed subcutaneous dosing. Propensity score matching (1:1) was performed using clinically relevant baseline variables. Outcomes included bleeding, thrombotic events, platelet recovery, and mortality. Results: Among 148 eligible patients, 96 received fondaparinux and 52 argatroban. After propensity score matching, 94 patients (47 per group) were included. Of these, 33 (22.3%) had confirmed HIT based on PF4 ELISA positivity, while 115 (77.7%) were classified as suspected HIT, defined as patients with negative or unavailable PF4 testing but clinical features consistent with HIT, including platelet count dynamics, with a similar distribution between groups. Overall, 28 patients (29.8%) were hemodynamically unstable at anticoagulation initiation. Baseline characteristics were generally well balanced after matching, although serum creatinine remained higher in the argatroban group. No statistically significant differences were observed between fondaparinux and argatroban in major bleeding (4.3% vs. 12.8%; adjusted OR 4.03, 95% CI 0.64-25.49), thrombotic events (2.1% vs. 10.6%; adjusted OR 5.07, 95% CI 0.55-46.48), or platelet recovery (87.2% vs. 76.6%; adjusted OR 0.36, 95% CI 0.11-1.19). ICU mortality was numerically higher in the argatroban group (40.4% vs. 19.1%; adjusted OR 3.02, 95% CI 1.14-7.96), whereas in-hospital mortality and length of stay were comparable. Conclusion: Fondaparinux demonstrated comparable safety and effectiveness to argatroban in patients with suspected or confirmed HIT. The higher ICU mortality observed in the argatroban group may reflect residual confounding related to illness severity and renal dysfunction. These findings suggest that fondaparinux may be a reasonable alternative in selected patients, while emphasizing individualized anticoagulant selection.