Low-molecular-weight heparin non-superior to standard therapy in reducing miscarriages


The most common thrombophilia types were heterozygosity for factor V Leiden, prothrombin 20210A mutation, and protein S deficiency.

Low-molecular-weight heparin (LMWH) did not increase the live-birth rate in comparison to standard therapy for pregnant women.

A team, led by Siobhan Quenby, MD, PhD, Biomedical Research Unit in Reproductive Health, University of Warwick, compared the 2 treatments in a cohort of pregnant women in several countries.

The data was presented during the American Society of Hematology (ASH) Annual Meeting and Exposition.


Recent research has identified an association between recurrent miscarriage and inherited thrombophilia.

“It has been hypothesized that anticoagulant therapy might reduce both number of miscarriages and adverse pregnancy outcomes in these women and this is widely practiced despite lack of solid evidence,” the authors wrote.

However, there are not many randomized controlled trials assessing the efficacy of low-molecular-weight heparin (LMWH) therapy in women with recurrent miscarriage and inherited thrombophilia.

In the investigator-initiated, international open-label randomized, controlled ALIFE 2 trial, the investigators examined patients at 15 hospitals in the Netherlands, US, Belgium, and Slovenia coordinated by the Netherlands. In addition, the UK coordinated 26 sites in England, Scotland, Wales, and Northern Ireland. Each participant was aged 18-42 years who had 2 or more pregnancy losses and confirmed inherited thrombophilia (factor V Leiden, prothrombin 20210A mutation, antithrombin, protein C or protein S deficiency).The participants were actively trying to conceive or were less than 7 weeks pregnant.

The exclusion criteria included women who were pregnant for 7 weeks or more, women that had an indication for anticoagulant treatment during pregnancy, those that had a contraindication for LMWH, individuals with a known allergy for LMWH, or those previously enrolled in the trial.

In the study, each participant was randomly assigned to use subcutaneous LMWH (n = 164) once daily with enoxaparin 40 mg, dalteparin 5000 IU, tinzaparin 4500 IU or nadroparin 3800 IU or standard pregnancy surveillance (n = 162) once they had a positive urine pregnancy test. The mean age of the patient population was 33 years.

The treatment began at the 7 week mark of pregnancy and continued until the end of the pregnancy.

The investigators sought primary outcomes of live birth rate and secondary outcomes of adverse pregnancy outcomes, including miscarriage, congenital malformations, obstetric complications such as premature delivery, pre-eclampsia, HELLP syndrome, and intrauterine growth restriction.

They also sought safety outcomes, including bleeding episodes, thrombocytopenia, and skin reactions to the prescribed study medication.

Birth Rates

Between August 2012 and January 2021, there were 10,626 women with recurrent miscarriage assessed for eligibility. However, the majority of patients were not eligible because of an absence of inherited thrombophilia. A total of 428 participants were eligible, 326 of which conceived and were randomized into 1 of the 2 treatment groups.

Prior to randomization, the median number of miscarriages was 3 and 70% of the patient population had a history of 3 or more miscarriages.

The most common thrombophilia types were heterozygosity for factor V Leiden (56%), prothrombin 20210A mutation (25%), and protein S deficiency (14%).

Aspiring was also used a co-medication for 11% of the patient population.

The overall live birth rate was 71.6% (n = 116) in the LMWH group and 70.9% (n = 112) in the standard surveillance group (aOR, 1.08; 95% CI, 0.65-1.78) (absolute difference, 0.7%; 95% CI, -9,2% to 10.6%).

Adverse events were identified in 23.8% (n = 39) of the LMWH group and 22.8% (n = 37) of the surveillance group.

“Compared with standard surveillance, the use of LMWH did not result in higher live birth rates in women who had two or more pregnancy losses and confirmed inherited thrombophilia,” the authors wrote. “On the basis of our findings, we do not advise routine use of LMWH in women with recurrent pregnancy loss and confirmed inherited thrombophilia, and we advise against routine testing for inherited thrombophilia in women with recurrent pregnancy loss.”

The study, “LBA-5 Low-Molecular-Weight Heparin Versus Standard Pregnancy Care for Women with Recurrent Miscarriage and Inherited Thrombophilia (ALIFE2): An Open-Label, Phase III Randomized Controlled Trial,” was published online by ASH 2022.

This article originally appeared on HCP Live Network®.

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