Safety of Fondaparinux After Low-Molecular-Weight Heparin in Bleeding-Complicated High-Risk Pregnancies: A PSM Cohort Study

Background: High-risk pregnancies (those complicated by antiphospholipid syndrome, rheumatic disease, or adverse obstetric histories) increase the risk of thromboembolic events, for which low-molecular-weight heparin (LMWH) is commonly used. However, LMWH can cause bleeding complications, leading to consideration of alternative anticoagulants. Fondaparinux (FPX), a selective factor Xa inhibitor, has been suggested as an alternative, but its safety and efficacy in pregnancy remain unclear. This study aimed to compare maternal and neonatal outcomes between high-risk pregnant women switched from LMWH to FPX due to bleeding complications and those who continued LMWH. Methods: A retrospective cohort study was conducted at a tertiary hospital from January 2018 to June 2024. Pregnant women on LMWH who developed LMWH-related bleeding were switched to FPX and resumed LMWH once bleeding resolved. The comparison group consisted of women who continued LMWH without complications. After propensity score matching (PSM), maternal and neonatal outcomes were compared between the two groups using chi-square tests for categorical variables and rank-sum tests for continuous variables. Results: A total of 159 high‑risk pregnant women were included before propensity score matching (124 in the LMWH group and 35 in the FPX group). After 2:1 matching, 62 patients (40 receiving LMWH and 22 receiving FPX) were analyzed with well‑balanced baseline characteristics between groups. In the matched cohort, rates of miscarriage, gestational age at delivery, live birth, Apgar scores, and neonatal intensive care unit admission were comparable between the two groups (all p > 0.05). Postpartum blood loss within 48 hours was significantly lower in the FPX group (p = 0.016), whereas neonatal birth weight was modestly lower (p = 0.019). Overall, FPX demonstrated a safety profile comparable to LMWH without an increase in adverse maternal or neonatal outcomes. Conclusion: The results are suggestive that FPX may be a safe and effective alternative for pregnant women intolerant to LMWH, associated with reduced postpartum hemorrhage and no increase in adverse outcomes. Further validation through multicenter and prospective studies is needed.