Low molecular weight heparin use during pregnancy and risk of postpartum hemorrhage: a systematic review and meta-analysis

Introduction: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide with a prevalence rate of approximately 6%. Although most cases of PPH have no identifiable risk factors, the incidence of PPH has been associated to the thromboprophylaxis in pregnancy with low molecular weight heparin (LMWH). Thus, the aim of the study is to evaluate the risk of PPH in cases of pregnant women exposed to LMWH.

Materials and methods: Electronic research was performed in OVID, Scopus, ClinicalTrials.gov, MEDLINE, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials through April 2016. We included randomized controlled trials, cohort and case-control studies of women who underwent thromboprophylaxis with LMWH during pregnancy compared to a control group (either placebo or no treatment). The primary outcome was the incidence of PPH. The summary measures were reported as relative risk (RR) or as mean differences (MD) with 95% confidence interval (CI).

Results: Eight studies including 22,162 women were analyzed. Of the 22,162 women, 1320 (6%) were administered LMWH, 20,842 (94%) women formed the nonexposed group (control group). Women treated with LMWH had a higher risk of PPH (RR 1.45, 95%CI 1.02–2.05) compared to controls; there was no difference in mean of blood loss at delivery (MD ?32.90, 95%CI 68.72–2.93) and in risk of blood transfusion at delivery (RR 1.24, 95%CI 0.62–2.51), respectively.

Conclusions: Women who receive LMWH during pregnancy have a significantly higher risk of developing PPH. Women who receive LMWH during pregnancy have neither significantly higher mean blood loss at delivery nor higher risk of blood transfusion.