Aspirin Plus Low-Molecular-Weight Heparin in Women with Recurrent Miscarriage

Published - Written by Karen Buckley

Approximately five percent of women trying to conceive have had two previous miscarriages, and one percent have had three. About half of these recurrent miscarriages are unexplained. Aspirin and low-molecular-weight heparin are often prescribed for women with unexplained recurrent miscarriage as standard treatment, based on the hypothesis that the condition might be caused by thrombosis in decidual vessels. However, data are lacking to support such use.

In the ALIFE study, Kaandorp et al. enrolled 364 women, ages 18-42 years, with a history of two or more miscarriages who were either trying to conceive or less than six weeks pregnant. They were randomized to receive daily aspirin, a combination of aspirin plus nadroparin (A low-molecular-weight heparin) , or placebo. Live birth rates did not differ significantly among the three study groups.

“This study underscores the need for careful evaluation of a therapy before widespread use. This randomized trial casts serious doubt on the utility of anticoagulant therapy in many women with a history of unexplained recurrent miscarriage, ” says Caren Solomon, M.D., deputy editor at NEJM.

While this study does not support the use of antithrombotic treatment in all women with a history of recurrent miscarriage, it was not powered to assess certain subgroups that might have a different response. Only 16% of the study participants had an identified thrombophilia. It is possible that such women might still benefit from this therapy. Some evidence suggests that women with the antiphospholipid syndrome, a condition that predisposes to thromboses and recurrent miscarriage, have improved pregnancy outcomes with aspirin and heparin, but the findings have been inconsistent. Further study of these groups is needed.

The authors conclude, “The concept that recurrent miscarriage can be attributed routinely to thrombosis is probably an oversimplification.”

In an accompanying editorial, Antithrombotic Therapy for Recurrent Miscarriage?, Dr. Ian Greer of York Medical School says, “The widespread use of antithrombotic interventions for women with two or more miscarriages appears to be no more than another false start in the race to identify an effective intervention for this distressing condition that affects so many women.”

Based on these findings, do you think it’s justified to discontinue the practice of treating women with a history of unexplained recurrent miscarriage with aspirin and heparin?