No improvement in the live birth rates was noted following daily administration of LMWH among women with history of recurrent miscarriages and inherited thrombophilia, according to the findings of the ALIFE 2 trial presented at the 64th Annual Meeting of the American Society of Hematology (ASH) held in New Orleans, Louisiana, USA.^1,2

A team of researchers from The Netherlands and the UK conducted an open-label randomized controlled international trial involving 428 women, mean age 33 years, between 2012 and 2021 with history of recurrent (≥2) miscarriages and diagnosis of inherited thrombophilia. Factor V Leiden was the most frequently occurring thrombophilia at 56% followed by prothrombin 20210A mutation (25%), protein S deficiency (14%) and combined thrombophilia in 3.6%.Women with gestational age of ≤ 7 weeks or those actively trying to conceive were included in the trial. The participants were selected from the Netherlands, USA, Belgium, Slovenia, England, Scotland, Wales and Northern Ireland. About 70% of the study subjects had a history of ≥3 abortions, with the median number of miscarriages being 3.

Out of the 428 women enrolled in the trial, 326 conceived; of these 164 were assigned to intervention with subcutaneous LMWH once daily (enoxaparin 40 mg, dalteparin 5000 IU, nadroparin 3800 IU or tinzaparin 4500 IU) coupled with standard pregnancy care, while 162 women received standard pregnancy care alone. LMWH was administered until the end of the pregnancy. The participants were followed up for up to six weeks post-delivery.

Results did not show significant differences in the live birth rate, which was the primary outcome measure of the trial; ~72% (16/162) in the LMWH group and ~71% (112/158) in the standard pregnancy alone group with an adjusted odds ratio of 1.08.

Occurrence of adverse events in the form of bleeding episodes, thrombocytopenia and local skin reactions was also comparable between the two groups; 44% among women taking a blood thinner vs 27% among those receiving standard care. The higher number of adverse events in the LMWH group was mainly due to localised skin reactions at the injection site.

This study has shown that taking a LMWH offered no extra advantages in improving live birth rates among women with recurrent pregnancy loss and confirmed inherited thrombophilia vs standard pregnancy care alone. Therefore, the researchers do not advocate routine testing for thrombophilia in this group of pregnant women. Testing for thrombophilia is expensive and so may be inaccessible to many women, particularly in resource-crunched countries. And, daily administration of the LMWH injections hampers quality of life.

References

1. Quenby S, et al. 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. Available at: https://ash.confex.com/ash/2022/webprogram/Paper171707.html, accessed on Dec. 27, 2022.
2. American Society of Hematology (ASH) Press Release, dated Dec. 13, 2022. https://www.hematology.org/newsroom/press-releases/2022/blood-thinners-during-pregnancy-made-no-difference-to-live-birth-rate-in-women, Accessed on Dec. 27, 2022.