Prophylaxis with low-dose low-molecular-weight heparin during pregnancy and postpartum: is it effective?

The optimal approach for venous thrombosis (VTE) prophylaxis during pregnancy and postpartum in women with an increased risk of VTE is not established. To evaluate the effectiveness, represented as the incidence of pregnancy-related VTE, and safety, represented as incidence of postpartum hemorrhage (PPH), of a protocol recommending prophylaxis with low-dose low-molecular-weight heparin (LMWH) in women at intermediate to high risk of VTE. In this retrospective cohort study, we analyzed 34 women (44 pregnancies) with intermediate risk of VTE who received low-dose LMWH for 6 weeks postpartum and 57 women (82 pregnancies) with high risk of VTE who received low-dose LMWH during pregnancy and for 6 weeks postpartum. Pregnancy-related VTE was defined as VTE during pregnancy or ≤ 3 months postpartum. PPH was defined as blood loss >500 mL and severe PPH as blood loss > 1000 mL. The incidence of pregnancy-related VTE was 5.5% (95% CI, 2.4-12.3) despite prophylaxis with low-dose LMWH. All events occurred in women at high risk, with a postpartum incidence of 7.0% (95% CI, 2.9-16.7) and antepartum incidence of 1.8% (95% CI, 0.4-9.2). The risk of PPH was 21.6% (95% CI, 14.3-31.3) and severe PPH 9.1% (95% CI, 4.7-16.9), which was not different in women who started LMWH postpartum and those who used LMWH during pregnancy. Although prophylaxis with low-dose LMWH during pregnancy and postpartum proved to be safe, the risk of pregnancy-related VTE is considerable in women with a high risk of VTE. VTE prophylaxis with low-dose LMWH may not be sufficiently effective in these women.

Roeters van Lennep JE ，Meijer E ，Klumper FJ ，Middeldorp JM ，Bloemenkamp KW ，Middeldorp S ... -  《-》

[Thromboprophylaxis with low-molecular-weight heparin insufficient in high-risk pregnancy].

Roeters van Lennep JE ，Meijer E ，Klumper FJ ，Middeldorp JM ，Bloemenkamp KW ，Middeldorp S ... -  《-》

Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Bates SM ，Greer IA ，Pabinger I ，Sofaer S ，Hirsh J ... -  《CHEST》

The incidence and risk factors of recurrent venous thromboembolism during pregnancy.

Recurrent venous thromboembolism (VTE) during pregnancy is a challenging topic with relatively few publications. The aim of this study was to identify the incidence and the risk factors of recurrent antepartum VTE in women with a history of at least one previous VTE episode. This observational cohort study involved 270 pregnant women (369 pregnancies) with at least one previous episode of VTE. The risk factors of recurrent antepartum VTE were identified by using group A (women without recurrent venous thromboembolism VTE) as a control group for group B (women with recurrent VTE despite LMWH (low molecular weight heparin) prophylaxis) and C (women with VTE recurrence in early pregnancy before the planned initiation of LMWH prophylaxis). The incidence of recurrent VTE was 7.6% (n=28). Twelve recurrent VTEs in ten women (3.3%) developed during early pregnancy before initiation of LMWH and sixteen recurrent VTEs (4.3%) developed in 15 women despite LMWH prophylaxis. In women with recurrent antepartum VTE, the incidence of a history of two or more previous VTEs (group A vs. B: 5.7% vs. 40.0%, p<0.001; group A vs. C: 5.7% vs. 30.0%, p=0.022), previous VTE in connection with antiphospholipid antibody syndrome (group A vs. B: 2.6% vs. 20.0%, p=0.012) and a history of VTE related to hormonal risk factors (group A vs. B: 60.4% vs. 93.3%, p=0.011) was significantly higher compared to those with successful LMWH-prophylaxis. The percentage of the women with long-term anticoagulation was also significantly higher among the women with recurrent antepartum VTE (group A vs. B: 7.6% vs. 46.7%, p<0.001) compared to those with successful LMWH-prophylaxis. The risk of antepartum recurrent VTE is considerable in women with a history of two or more previous VTEs, antiphospholipid antibody syndrome or long-term anticoagulation. The antepartum prophylaxis with prophylactic dose of LMWH or even with intermediate dose of LMWH might not be sufficient in this high-risk population.

Galambosi PJ ，Ulander VM ，Kaaja RJ 《-》

The risk of postpartum hemorrhage in women using high dose of low-molecular-weight heparins during pregnancy.

Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulant during pregnancy for prevention or treatment of VTE. However, the size of the associated risk of postpartum haemorrhage (PPH) is unknown. To assess the bleeding risk of high dose LMWH, also in relation to time between last dose LMWH and delivery. From 1999 to 2009, we followed 88 pregnant women who were started on therapeutic anticoagulation. Controls were pregnant women without LMWH, matched 1:4 for parity, mode of delivery, age, gestational age and delivery date. PPH was defined as >500 ml blood loss for vaginal delivery (severe PPH in vaginal delivery as >1000 ml) and >1000 ml for cesarean section (CS). Women were divided into subgroups by the interval between last dose of anticoagulation and delivery (<12, 12-24 hrs, >24 hrs). Risk of PPH after vaginal delivery was 30% and 18% for LMWH-users and non-users, respectively (OR 1.9, 95%CI 1.1-3.5). Risk of severe PPH after vaginal delivery was not different (5.6 vs 5.0%; OR 1.1; 0.4-3.6). Risk of PPH after CS was 12% in LMWH-users and 4% in non-users (OR 2.9; 0.5-19.4). Both events of LMWH-users occurred after emergency CS. The risk of PPH associated with delivery within 24 hours after last dose of LMWH was 1.2 fold higher (95%CI 0.4-3.6) compared to a larger interval. High dose LMWH carries an increased risk of more than 500 mL blood loss after vaginal delivery. However, this results not in more clinical relevant severe PPHs. The interval between last dose of LMWH and delivery does not influence the risk of PPH.

Knol HM ，Schultinge L ，Veeger NJ ，Kluin-Nelemans HC ，Erwich JJ ，Meijer K ... -  《-》