Thrombophilia, a tendency for excessive blood clotting, increases the risk of stillbirth because it interrupts the normal circulation of blood from the mother to the placenta. A team of researchers from two French institutions, the University Hospital in Nimes and the University of Montpellier 1, studied 160 pregnant women with genetic risk factors for thrombophilia (heterozygous factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency) who had experienced one unexplained stillbirth at 10 weeks gestation or later prior to the study.
Treatment for the women began in their eighth week of the new pregnancy. Eighty participants were provided with 40 mg of enoxaparin by subcutaneous injection each day. Because of ethical concerns regarding providing pregnant women with a placebo, the researchers instead provided the other 80 participants with low-dose aspirin (100 mg daily), a commonly used blood thinner. All participants were also given 5 mg of folic acid a day as an additional preventive measure, beginning at least one month prior to conception and continuing throughout the pregnancy.
The results of enoxaparin use were impressive. Of the women on the drug, 86 percent had a normal live birth. In addition, no significant side effects were seen in these mothers or their newborns. The group taking aspirin suffered 57 pregnancy losses and only 29 percent of the women taking this medication had a successful birth.
The enoxaparin babies also weighed more than those born to the mothers taking aspirin; only 10 percent of enoxaparin newborns were small for their gestational age, compared with 30 percent of the aspirin newborns. Low birth weight is associated with a greater risk of severe health problems, such as coronary heart disease and developmental disability.
According to Jean-Christophe Gris, M.D., Ph.D., of the University Hospital and lead author of the study, "For women with a prior pregnancy loss and a genetic predisposition to thrombophilia, treatment with enoxaparin is associated with a much greater chance of live birth and a normal-weight baby, without adverse side effects."
"The studies reported by Dr. Gris and colleagues from Nimes and Montpelier are the first to provide evidence that therapy using the anticoagulant enoxaparin significantly reduces the pregnancy loss rate associated with genetic thrombophilia compared with women treated with low-dose aspirin," said Kenneth G. Mann, Ph.D., Professor and Chairman of the Department of Biochemistry at the University of Vermont. "Although additional randomized clinical trials are needed before recommending enoxaparin therapy for the routine management of pregnant women with these specific thrombophilia disorders, the compelling results of this study and the relatively benign nature of the therapy support the potential of a wider application in treating individuals with recurrent fetal losses due to genetic thrombophilias."
This work was supported by grants from Diagnostica Stago, Biopep S.A., and Baxter Healthcare Corporation.
To receive a copy of the study or to arrange an interview with Jean-Christophe Gris, M.D., Ph.D., lead author of the study, please contact Aislinn Raedy at 202-776-0544 or araedy@hematology.org.
The American Society of Hematology (www.hematology.org) is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.
Blood, the official journal of the American Society of Hematology, is the most cited peer-reviewed publication in the field. Blood is issued to Society members and other subscribers twice per month, available in print and online at www.bloodjournal.org.
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