The routine use of low molecular weight heparin (LMWH) did not improve the rates of live births among women with inherited thrombophilia who had experienced 2 or more pregnancy losses in the past, according to results of an investigator-initiated phase 3 study presented at the 2022 ASH Annual Meeting.
“This is the first randomized controlled trial dedicated entirely to women with recurrent miscarriages and inherited thrombophilia,” Saskia Middeldorp, MD, of the Radboud University Medical Center in Nijmegen, The Netherlands, said when presenting the results of the study.
The open-label, phase 3 ALIFE2 trial randomly assigned 326 women with inherited thrombophilia and a history of pregnancy loss to receive self-administered, subcutaneous LMWH or standard surveillance for the duration of their pregnancy. The primary endpoint was live birth rate and secondary outcomes included adverse pregnancy outcomes, complications, and congenital malformations.
The mean age at baseline was 33 and 83% of patients were Caucasian. The median number of prior miscarriages was 3, with 70% of patients having a history of 3 or more. Heterozygosity for factor V Leiden was present among 57% of patients, prothrombin 20210A mutation among 26%, and protein S deficiency among 14%.
There was no significant difference in live birth rates between the groups, at 71.6% with LMWH and 70.9% with surveillance only (adjusted odds ratio [OR], 1.08; 95% CI, 0.65-1.78; P =.770).
Dr Middeldorp noted that there was also no significant difference in live birth rates between the groups for other secondary outcomes, including preeclampsia or small for gestational age.
Adverse events (AEs) occurred more frequently with LMWH with a rate of 43.9% compared with 26.5% with surveillance. The most common AEs with LMWH were easy bruising, injection-site skin reaction, and minor bleeding.
“There were no differences in major bleeding or other more serious adverse effects,” Dr Middeldorp said. She then concluded that these results indicate that LMWH should not be used to treat women with thrombophilia “with the aim to prevent miscarriage.”
Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Quenby S, Booth K, Hiller L, et al. 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. Presented at ASH 2022. December 10-13, 2022. Abstract LBA-5.