Study in ASH Late-Breaking Abstracts session: Blood Thinners During Pregnancy Made No Difference to Live Birth Rate in Women with Recurrent Miscarriage and Inherited Thrombophilia

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

In an international randomized trial, daily injections of a blood thinner during pregnancy did not increase the rate of live births among women with an inherited blood clotting disorder who had experienced two or more previous miscarriages, according to data presented during the 64th American Society of Hematology (ASH) Annual Meeting and Exposition.

Previous research suggests that people with inherited thrombophilia are at increased risk for experiencing blood clots. Observational studies have shown an association between inherited thrombophilia and recurrent miscarriage, potentially due to clots in the developing placenta, said Saskia Middeldorp, MD, PhD, of Radboud university medical center and the study’s principal investigator. For this reason, she said, many doctors treat pregnant women who have inherited thrombophilia with injectable blood-thinning medications to try to reduce their risk of miscarriage, although no randomized controlled trials – the “gold standard” of medical research – had shown that such treatment was effective.

“Recurrent miscarriage is a devastating condition for women and their partners,” Dr. Middeldorp said. “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 evidence that this improves their chances of having a successful pregnancy.”

Testing for thrombophilia and blood thinners is costly, and self-administering daily injections of a blood thinner is also burdensome and negatively affects quality of life.

“Side effects such as bruising at injection sites are common. We believed it was important to determine in a randomized controlled trial whether this treatment was actually helping patients,” Dr. Middeldorp added.

The study, known as ALIFE2, enrolled 428 women with inherited thrombophilia and a history of miscarriage who were again trying to become pregnant. Their average age was 33 and 83% were white; 70% had had three or more miscarriages. A total of 326 women conceived and were randomly assigned to receive either standard pregnancy care (i.e., regular prenatal visits and testing, including ultrasound exams) plus a once-daily self-administered injection of a blood thinner or standard pregnancy care alone. Those in the blood-thinner group were instructed to stop their daily injections when they experienced the first signs of labor. All study participants were followed up until six weeks after giving birth. Six women (two in the blood thinner group and four in the standard care group) were lost to follow-up or dropped out during the study.

The study’s primary outcome was the rate of live births in the two groups. Results showed that these were nearly identical: 71.6% in the blood thinner group compared with 70.9% in the standard -care group. Women experiencing adverse events, such as bleeding, a drop in platelet count (platelets are the components of red blood cells that help the blood to clot), itching, bruising, or swelling, differed between the two groups: 44% among those taking a blood thinner compared with 27% among those receiving standard care. The difference could mainly be attributed to bruising and skin reactions around the injection site.

Because the study showed that taking a blood thinner did not improve pregnancy outcomes, Dr. Middeldorp said, she and her research team also recommend against routine testing for thrombophilia in this population of pregnant women. “Testing for thrombophilia is costly and should only be done if it will have therapeutic consequences,” she said.

The study’s findings should be reassuring for women with thrombophilia who have experienced multiple miscarriages, she said. “It’s important to keep in mind that approximately one in three to four 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].”

The study has some limitations, Dr. Middeldorp said. The study was relatively small, though it was an accomplishment to enroll so many pregnant women; most women (83%) were white. Secondly, because the study was not blinded, both the women and their doctors knew which treatment group (blood thinners or standard care alone) each woman was assigned to. Thirdly, 18 women who were randomly assigned to standard care were switched to the blood thinner group before 12 weeks of pregnancy, i.e., during the window when miscarriage could still occur. However, an analysis that excluded these women did not change the study’s conclusions, Dr. Middledorp said.

The study was coordinated by Warwick University UK, and Amsterdam UMC, University of Amsterdam the Netherlands and funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-1013-32011, awarded to S. Quenby) and by theOrganization for Health Research and Development (NWO, VIDI innovative research grant 016.126.364 awarded to S. Middeldorp).

Saskia Middeldorp, MD, PhD, will present this study on Tuesday, December 13, 2022, at 9:00 a.m. Central time in Hall E.

Additional press briefings took place throughout the meeting on pediatric cancer care, advances in blood cancer research and care, novel drug development, and health equity. For the complete annual meeting program and abstracts visit www.hematology.org/annual-meeting. Follow ASH and #ASH22 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2022 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH’s flagship journal, Blood (www.bloodjournal.org), is the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), is the Society’s online, peer-reviewed open-access journal.

Contacts:

Leah Enser, ASH, [email protected]
Kira Sampson, ASH, [email protected]
Brianne Cannon, FleishmanHillard, [email protected]