The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism during pregnancy and postpartum is uncertain. An open-label randomized controlled study was undertaken to investigate the efficacy and safety of intermediate-dose versus low-dose low-molecular-weight heparin in pregnant women with a history of venous thromboembolism.

Pregnant women ages 18 or older were eligible for the study if they had a history of objectively confirmed venous thromboembolism and were at 14 weeks or less of gestation. A total of 1,110 women were enrolled and randomly assigned to either the intermediate-dose or low-dose low-molecular-weight heparin group.

The primary efficacy outcome-symptomatic venous thromboembolism from randomization up to six weeks postpartum-occurred in 2% of women in the intermediate-dose low-molecular-weight heparin group and in 3% of those in the low-dose low-molecular-weight heparin group, a nonsignificant difference. In the antepartum period, venous thromboembolism occurred in 1% of the women in each group, whereas in the postpartum period, venous thromboembolism occurred in 1% of women in the intermediate-dose group and in 2% of women in the low-dose group. The primary safety outcome of major bleeding from randomization up to six weeks postpartum occurred in 4% of women in both the intermediate-dose and low-dose groups.

There were some noteworthy differences between the treatment groups: the risk of pulmonary embolism was substantially lower in the intermediate-dose group, venous thromboembolism or superficial thrombophlebitis occurred in 2% of women in the intermediate-dose group compared with 5% of those in the low-dose group, and a potential differential effect of the intervention was observed in the antepartum versus postpartum period.

The study had several limitations, including the lack of a placebo group, protocol deviations, and reliance on self-reported adherence.