Prophylactic-dose low molecular weight heparin (LMWH), with or without aspirin, did not reduce the risk of pregnancy loss in women with inherited thrombophilia and a history of prior late or recurrent early pregnancy loss, based on a meta-analysis of randomized, controlled trials.
“To our knowledge, this is the largest study published to date that evaluates LMWH in women with inherited thrombophilia and previous pregnancy loss,” Dr. Leslie Skeith, of the University of Ottawa, and her colleagues wrote in Blood (2016 Mar 31;127[13]:1650-55). A recent Cochrane Review (2014 Jul 4;7:CD004734) similarly found no difference in live birth rates in women with or without inherited thrombophilia treated with LMWH and aspirin, compared with women given no treatment. Additionally, the Effects of Aspirin in Gestation and Reproduction [EAGeR] trial found no difference in live birth rates in women with previous pregnancy loss given aspirin or placebo (Lancet. 2014;384[9937]:29-36).
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Based on a literature search, 8 publications and 483 participants met eligibility criteria as randomized, controlled trials for the meta-analysis. Four trials included an LMWH-plus-aspirin arm, and five trials included an LMWH-only arm. The control groups included four trials with an aspirin arm, and five trials with a placebo or no-treatment arm. The data indicated no difference in the treated groups and controls (relative risk of 0.81; 95% confidence interval, 0.55-1.19; P = .28).
As there is the potential for adverse side effects and significant cost with LMWH, the researchers advise against the use of LMWH to prevent recurrent and prior late pregnancy loss (greater than 10 weeks gestation) in women with inherited thrombophilia (Grade 1B, strong recommendation with moderate-quality evidence) and suggest against LMWH to prevent recurrent pregnancy loss in women with inherited thrombophilia and prior recurrent early (less than 10 weeks) pregnancy loss. (Grade 2B, weak recommendation with moderate-quality evidence.)
Given that the analysis included just 66 women with thrombophilia and prior recurrent early pregnancy loss, the researchers could not exclude a beneficial effect of LMWH in this subgroup. An ongoing randomized controlled trial, ALIFE2 (Netherlands Trial Registration Identifier: NTR3361), “is evaluating LMWH in women with inherited thrombophilia and a history of two or more miscarriages and/or intrauterine fetal death, which we hope will provide definitive answers to this question,” the researchers wrote.
They also suggest not testing for inherited thrombophilia in women with prior late or recurrent early pregnancy loss (Grade 2B, weak recommendation with moderate-quality evidence).
The study was supported by a series of university and institutional investigator research awards. Dr. Skeith received a Thrombosis Canada CanVECTOR Research Fellowship award.
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