Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin: results of a retrospective cohort study

Abstract

BackgroundLow-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in a retrospective controlled cohort.MethodsAll pregnant women who received therapeutic doses of LMWH between 1995 and 2008 were identified in the Academic Medical Center, Amsterdam, The Netherlands. The controls were women registered for antenatal care in the same hospital who did not use LMWH during pregnancy, matched by random electronic selection for age, parity and delivery date to LMWH users. The incidence of PPH (blood loss >500 ml), severe PPH (blood loss >1000 ml) and median blood loss were compared in two cohorts of LMWH users and non-users.ResultsThe incidence of PPH was 18% in LMWH users (N=95) and 22% in non-users (N=524) (RR 0.8; 95% CI 0.5 to 1.4). The incidence of severe PPH was 6% in both groups (RR 1.2; 0.5 to 2.9). The median amount of blood loss differed only in normal vaginal deliveries. It was 200 ml in LMWH users and 300 ml in non-users (difference −100 ml; 95% CI −156 to −44).ConclusionTherapeutic doses of LMWH in pregnancy were observed not to be associated with a clinically meaningful increase in the incidence of PPH or severe PPH in women delivered in this hospital, although this observation may be confounded by the differential use of strategies to prevent bleeding. A randomised controlled trial is necessary to provide a definite answer about the optimal dose of LMWH in pregnancy.

A double centre retrospective study into rates of postpartum haemorrhage in women on low molecular weight heparin

“…Roshani et al (2011) observed that therapeutic dose of LMWH was not associated with a clinically meaningful increase in PPH or severe PPH in 95 women delivered in their hospital. Knol et al (2012) concluded from their study of 88 women that high dose LMWH was associated with an increased risk of >500 ml blood loss after vaginal delivery (30% as compared to 18% in non-users) and that the risk of severe PPH after caesarean section was 12% in LMWH users and 4% in non-users.…”

Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: Rationale and design of the Highlow study, a randomised trial of two doses

“…It has been postulated that an intermediate dose of LMWH could have superior efficacy compared to a prophylactic dose of LMWH, but potentially at the cost of a higher bleeding risk. Reassuringly, in a retrospective study in pregnant women receiving therapeutic doses of LMWH, there was no increased risk of clinically relevant or severe postpartum bleeding compared with women who had delivered in the same hospital without LMWH use [20]. In another study, women receiving therapeutic LMWH during pregnancy were found to have an increased risk of blood loss N500 mL and b1000 mL after vaginal delivery [21].…”

Cardiovascular Management in Pregnancy

“…58 However, a recent small study confirms earlier observations of neonatal anti-factor Xa levels at ≈10% of maternal levels. 45,59 This raises the possibility that fondaparinux may cross the human placenta in small doses. Prior studies on the safe and effective use of fondaparinux have used the same weight-based prophylactic and therapeutic doses used in the nonpregnant population.…”

“…44 The lack of increase in postpartum hemorrhage among pregnant women using enoxaparin is supported in other studies. 45 The theoretical potential for increased bleeding may be mitigated by strategic timing of doses relative to labor and delivery. The blood loss among women using LMWH may be reduced by stopping therapy 24 hours before the onset of labor or converting to UFH as described above.…”