For the past 20 years pregnant women with an increased risk of developing blood clots have often been prescribed a common blood thinner to prevent serious complications from the clots, including preeclampsia (high blood pressure in the mother), disruption of the placenta, low birth weight and loss of the fetus. The largest randomized clinical trial to examine the therapy finds that the drug—low-molecular-weight heparin—is not effective. The find, reported in The Lancet, is the result of a dozen years of analysis of patients across five countries.
Clots are clumps of blood cells, platelets and proteins, and so it seemed logical to think that diluting, or thinning, the blood with heparin would give the clotting components less opportunity to cluster. The treatment seemed especially appealing for pregnant women with thrombophilia, who start off at elevated risk of developing blood clots because of inherited or acquired conditions. “These complications can be so devastating from a patient perspective that anything that provides hope seems pretty compelling to use,” says lead author Marc Rodger, a hematologist at the University of Ottawa and the Ottawa Hospital Research Institute.
The investigation found that a heparin regimen, which is administered by injection, did not reduce the incidence of serious blood clots, miscarriage or stillbirth among women deemed to be at increased risk of developing clots based on known thrombophilia and past experiences during pregnancy. Overall, the study authors wrote, these findings coupled with earlier work indicate that heparin does not prevent recurrent pregnancy loss and that a family history of venous thromboembolisms (blood clots in veins) is not enough reason to take heparin injections during pregnancy. Furthermore, widespread belief in the merit of this ineffective therapy prevents researchers from thinking they need to look into other potential treatment options, the authors say.
This study compared pregnancy outcomes among 292 women randomized to either receive heparin or not. Those receiving the drug injected themselves each day until 37 weeks into their pregnancies, beginning at 20 weeks into pregnancy or earlier. In the U.S. the therapy can cost more than $8,000 per pregnancy; the number of women treated yearly is unknown.
The authors examined whether the drug helped reduce a variety of pregnancy complications as a whole, rather than scrutinizing its effects on venous thromboembolism, preeclampsia and other problems individually. They took this tack because they were unable to recruit the number of subjects needed to obtain statistical significance for each medical problem. Many women were apparently reluctant to enroll in the study for fear of being assigned to a treatment plan they did not prefer.
Katherine Economy, a maternal fetal medicine specialist at Brigham and Women’s Hospital in Boston, says that the new work convinced her that she “should probably give less weight to some of the experiential data that suggests anticoagulation would be helpful in preventing preeclampsia.” Still, she cautions that in allowing patients to start the drug as late as 20 weeks into pregnancy the protocol may not have been ideal for exploring whether the drug helps prevent preeclampsia; experts in placental development often suggest starting with a blood thinner as early as eight weeks, she says. What’s more, the women in both the heparin and control groups also received injections of the drug for 42 days after birth, potentially helping to protect them against blood clots that may manifest themselves at that point, but possibly diluting the results—making it appear that heparin was not as effective as it may have been.
Keith Eddleman, director of obstetrics at Mount Sinai Hospital in New York City, says the new findings confirm earlier work but that he, too, cautions that the results are not definitive for all patients. Heparin, he adds, may still be a good fit for some pregnant women with serious types of thrombophilia. Eddleman was not involved with the study.
Further analysis of each individual condition could reveal that heparin alone or in combination with other drugs, such as aspirin, may help to prevent one or more of those conditions in women who had, say, prior severe preeclampsia or who gave birth to a child with severe low birth weight. But because enrolling patients for the study was so difficult, Rodgers says, it may be challenging to find out anytime soon.
“A lot of patients and physicians jumped on the bandwagon with heparin,” he notes. “Based on our study and our synthesis of the literature, I think that now we should really put this medication back on the shelf and look at other [drugs].”