Low molecular weight heparin therapy during pregnancy is associated with elevated circulatory levels of placental growth factor

Introduction Low molecular weight heparin (LMWH) has been shown to be effective in decreasing the recurrence of placenta-mediated complications of pregnant women. The aim of this study was to determine the effect of LMWH on circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PLGF) in pregnant women who required anticoagulation therapy. Methods A longitudinal prospective cohort study was performed including pregnant women in whom anticoagulation therapy by LMWH during pregnancy was clinically indicated (n = 33). Healthy pregnant women, matched for gestational age, who did not require thromboprophylaxis served as controls (n = 29). Maternal plasma samples were obtained throughout gestation every 4 weeks and stored at -70 °C. Maternal plasma concentrations of sFlt-1, sEng and PLGF were determined by ELISA and compared between the two groups. Results Patients treated with LMWH had significantly increased circulatory levels of PLGF during the third trimester compared with controls (28-34 weeks: 719.2 pg/ml vs 558.6 pg/ml at, p < 0.01; 35-40 weeks: 975.6 pg/ml vs 511.2 pg/ml, p < 0.01, respectively). In contrast, circulatory levels of sFlt-1 and sEng were similar between the LMWH treatment group and controls throughout gestation. Consistent with these findings, the ratio of sFlt-1/PLGF was lower in patients treated with LMWH compared to controls (28-34 weeks: 1.9 vs 7.2, p < 0.05; 35-40 weeks: 5 vs 12.9, p < 0.05, respectively). Discussion Anticoagulation treatment of pregnant women with LMWH is associated with a pro-angiogenic state. These findings may explain the effectiveness of LMWH in the prevention of placenta-mediated complications of pregnancy.