Effect of prophylactic subcutaneous unfractionated heparin on the maternal sFlt-1/PlGF ratio: a retrospective cohort study

BACKGROUND: The ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) is widely used to assess the risk of preeclampsia. However, heparin can transiently increase the level of circulating sFlt-1, making it unclear whether prophylactic subcutaneous unfractionated heparin (UFH)-commonly used for thromboprophylaxis in pregnancy-affects the reliability of this biomarker. METHODS: We conducted a retrospective cohort study to compare mid-trimester (18w0d-23w6d) sFlt-1 levels and sFlt-1/PlGF ratios in 45 pregnant women receiving prophylactic subcutaneous UFH for antiphospholipid syndrome or a history of thrombosis and 563 controls. We also examined the association between biomarker levels and time elapsed since the last UFH injection. RESULTS: Mid-trimester sFlt-1 levels (1900 vs. 1782 pg/mL, p = 0.15) and sFlt-1/PlGF ratios (7.2 vs. 6.7, p = 0.87) were equivalent between the UFH and control groups. Multivariate regression analysis adjusting for maternal age, body mass index, gestational age at sampling, and low-dose aspirin intake confirmed no significant association between prophylactic UFH and sFlt-1 levels or sFlt-1/PlGF ratios. Within the UFH group, no correlation was found between the time since administration (range 63-477 min) and sFlt-1 levels (r=-0.049, p = 0.75) or sFlt-1/PlGF ratios (r = 0.019, p = 0.90). CONCLUSION: Prophylactic subcutaneous UFH was not associated with significant differences in sFlt-1/PlGF ratios, and the serum levels were not correlated with the timing of administration within the examined window. These findings suggest that the sFlt-1/PlGF ratio may remain a reliable tool for preeclampsia risk assessment in women receiving UFH prophylaxis under routine clinical sampling conditions.