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

Posted by • March 24th, 2010

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?

6 Responses to “Aspirin Plus Low-Molecular-Weight Heparin in Women with Recurrent Miscarriage”

  1. Trina says:

    I hope you don’t mind a response by a layperson. While I certainly don’t want to discourage further research on recurrent miscarriage, as a woman who experienced 2 miscarriages before delivering healthy twins, giving a treatment with even a small percentage of success is preferable to just hearing the words ‘try again.’ On my fourth round of IVF, my RE, rheumatoligist and I worked to find treatment for my apparent recurrent miscarriage and hit upon a solution that involved the use of aspirin, prednisone, folic acid and progesterone. this treatment was part of a study where women with recurrent miscarriage treated with these drugs during conception and the first trimester of their pregnancies were significantly more successful in maintaining their pregnancies than a control group. i strongly believe that this treatment enabled me to deliver two healthy babies with minimal complications. Just feeling that I was doing everything I could to take control of the situation made all the difference for me psychologically as well.

  2. Hanif Khan says:

    Certainly not. Although I do not use any sort of heparin, I routinely prescribe aspirin to women concerned with their pregnancy loss(es). Since aspirin is so cheap and there is a minimal risk of side-effects (I have not noted any over the last 15 years), plus with its possible beneficial effects, aspirin therapy certainly poses multiple benefits. At the very least, it serves to allay patient anxiety and strengthen their resolve. However, I would not prescribe heparin unless there is evidence of anti-phospholipid syndrome or such similar causal aetiology.

  3. Susumu Inoue says:

    I beleive that it is justified to stop these medications after work/up for sognificant thromophilic conditions turned out to be negative including phoholipid antibodies. I am not an obstetrician, so I don’t know the current standard of practice. But, it seems to me that at least some standard work-up needs to be done to exculde conditions associated with high risk miscarriges.

  4. Josh Grossman Col {r} USAR MC MD FACP says:


  5. i have a lot of this cases,i never put aspirin,or anything else.first we ask for antiphopholipids,is +,we began to use aspirina and enoxiparina,if not we put methilprednisolone one for month.
    well even antiphospholipids not always is not an abortion,we decide begin to put methilprenisolone to every woman and they are better than anything else

  6. D. Hewitt, M.D. says:

    I am surprised that these studies have more-or-less blindly enrolled these women without regard to their actual thrombophilic status. It would be easy to determine risk of thrombosis using TEG with PlateletMapping. Those who are at risk for thrombosis due to enzymatic abnormality could be given Lovenox; those with platelet hypersensitivity could be given the antiplatelet agent of the week. The studies of Regan and Rai from St. Mary’s in London were performed before PlateletMapping was available, but they identified patients at risk. I have not seen follow-up data based on treatment protocols.