January/February 2023
Thromboprophylaxis in pregnancy: what dose of low-molecular-weight heparin is best?

A single daily low dose of LMWH was safe and effective in women with previous venous thromboembolism.

For women in early pregnancy with prior venous thromboembolism (VTE), we must balance our thromboprophylaxis decisions between risk for recurrent VTE and risk for major bleeding. Data to inform such decisions have largely been extrapolated from studies of nonpregnant women, with limited understanding of how physio­logical changes of pregnancy affect efficacy.

In this multicentre international trial, investigators randomised 1110 pregnant women with prior VTE (defined as ‘unprovoked or provoked by hormonal or minor risk factors’) to either low­-dose or intermediate­-dose low­-molecular­-weight heparin (LMWH). All dosing was once daily and continued until six weeks postpartum (paused at time of delivery). Choice of LMWH varied by country, and dosing was dependent on the exact agent. For example, for enoxaparin (used in 38% of cases), the daily weight­-based low dose was 40 to 60 mg and the intermediate dose was 60 to 120 mg.

Key results are as follows:
• rates of symptomatic VTE (until six weeks' postpartum) were similar in the low­-dose and intermediate­-dose groups (2% vs 3%; p=0.33)
• five more VTE events in the postpartum period occurred in the low­-dose group (1%) than in the intermediate­dose group, but this difference was not statistically significant
• the rate of major bleeding was 4% in both groups
• no cases of heparin-induced thrombocytopenia occurred.  

Comment: These findings should reassure women and clinicians that a single daily dose of low­-dose LMWH is safe and effective for preventing recurrent VTE during pregnancy. Whether the post­partum findings of a slight VTE excess justify postpartum step­-up from a low dose to an intermediate dose is unclear and should be individualised.

Clinical Assistant Professor in Family Medicine, University of Michigan Medical School, Ann Arbor, USA.

Bistervels IM, et al. Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial. Lancet 2022; 400: 177-1787.

This summary is taken from the following Journal Watch title: Women’s Health