Daily LMWH Not Beneficial in Pregnant Women with Inherited Thrombophilia and Recurrent Miscarriage

TON - February 2023 Vol 16, No 1

The use of low-molecular-weight heparin (LMWH) did not improve the rate of live births among pregnant women with inherited thrombophilia and recurrent miscarriage, according to results of a clinical trial presented during the 64th American Society of Hematology Annual Meeting and Exposition.

The rate of live births was almost identical in women with inherited thrombophilia who were randomized to receive LMWH versus standard pregnancy surveillance—approximately 70%. These findings suggest that it is not beneficial to test for inherited thrombophilia in women with recurrent miscarriages or to prescribe LMWH with the aim of improving live birth rates.

Link Between Inherited Thrombophilia and Miscarriage

Women with inherited thrombophilia are at increased risk for blood clots, and observational studies have shown a link between inherited thrombophilia and recurrent miscarriage, potentially due to clots developing in the placenta. For this reason, it is common for physicians to prescribe prophylactic injectable blood thinners to pregnant women with inherited thrombophilia in an attempt to reduce their risk for miscarriage, but there is no solid evidence to support this practice.

“Recurrent miscarriage is a devastating condition for women and their partners. It has become common medical practice to test women experiencing recurrent miscarriage for inherited thrombophilia and to treat those found to have the condition with injectable blood thinners, despite absence of convincing evidence [from phase 3 randomized trials] that this improves their chances of having a successful pregnancy,” said Saskia Middeldorp, MD, PhD, Professor, Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands, who presented the late-breaking abstract at the meeting.

Dr Middeldorp explained that testing for thrombophilia and the daily use of self-administered thinners is costly and burdensome, which can negatively affect patient quality of life.

Study Details

The open-label, phase 3 ALIFE2 trial randomly assigned 326 women with inherited thrombophilia and a history of pregnancy loss to self-administered, daily doses of subcutaneous LMWH (ie, enoxaparin [Lovenox], dalteparin [Fragmin], tinzaparin [Innohep], or nadroparin [Fraxiparin]) after 7 weeks of pregnancy (and continued until the end of pregnancy) or standard surveillance for the duration of their pregnancy.

The mean age at baseline was 33 years and 83% of patients were white. The median number of previous miscarriages was 3, with 70% of patients having a history of ≥3 miscarriages. Heterozygosity for factor V Leiden was present among 57% of patients, prothrombin 20210A mutation among 26%, and protein S deficiency among 14%.

Women assigned to receive LMWH were instructed to stop their daily injections at the first signs of labor. All study participants were followed up until 6 weeks after giving birth. Six women (2 in the LMWH group and 4 in the standard care group) were lost to follow-up or dropped out during the study.

The primary end point was the rate of live births in the 2 groups, and these were almost identical: 71.6% in the LMWH group compared with 70.9% in the standard care group. Adverse events occurred more frequently with LMWH, with a rate of 43.9% compared with 26.5% with surveillance. The most common adverse events associated with LMWH were easy bruising, injection-site skin reactions, and minor bleeding.

Based on these findings, Dr Middeldorp and colleagues no longer recommend routine testing for thrombophilia in women who have frequently had miscarriages.

An important takeaway message from the study is that women with inherited thrombophilia who have miscarried twice or more can be optimistic about their chances of having a live birth.

“When counseling patients, it’s important to keep in mind that approximately 1 in 3 to 4 of all pregnancies ends in a miscarriage,” she said. “Our study showed that, with standard pregnancy care—and without expensive testing and burdensome medication use—slightly more than 70% of women had a live birth [which is what we typically see in the general population].”

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