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. Plain Language Summary: Pregnant women have a higher risk of developing blood clots, which can be dangerous for both mother and baby. To prevent these complications, doctors often use a medication called low-molecular-weight heparin (LMWH). However, some women experience bleeding problems while using LMWH. In such cases, it is important to find a safe alternative. This study looked at the use of another blood-thinning drug, fondaparinux (FPX), in women who had bleeding caused by LMWH. The results showed that FPX was as safe and effective as LMWH in preventing pregnancy complications. Women who used FPX had less bleeding after childbirth, and their babies were healthy overall, with similar outcomes to those whose mothers continued LMWH treatment. These findings suggest that FPX may be a useful alternative for pregnant women who cannot continue LMWH due to bleeding. This research provides practical information that can help doctors personalize treatment and improve safety for both mothers and newborns. Keywords: anticoagulation, fondaparinux, low-molecular-weight heparin, pregnancy, bleeding complications, neonatal outcomes