Therapy for women prone to miscarriage questioned

Blood-thinning treatments for pregnant women with an inherited condition that makes them susceptible to blood clots may do more harm than good, Danish researchers report.

Their study was designed to investigate the cause of repeat miscarriages in women with hereditary thrombophilia, a tendency to form blood clots, not the safety of particular treatments.

Nevertheless, in the course of that work they found little difference between women with or without the known gene mutations that cause thrombophilia, except for a higher likelihood of excessive bleeding during delivery among women carrying the mutations. The researchers attribute that heavy bleeding to the “standard practice” of administering blood thinners to pregnant women with thrombophilia.

The result “further emphasizes the need” to test the effect of blood thinners in women with repeated miscarriages and the genetic mutations that cause thrombophilia in a large clinical trial, Dr. Marie Lund of Copenhagen University Hospital’s fertility clinic told Reuters Health in an e-mail, “since it cannot be excluded that blood thinners to this group of women would in fact do more harm than good.”

At least five known gene mutations increase an individual’s tendency to form blood clots, but the most common of these is estimated to be present in about 8 percent of the population. Many carriers may never experience a problem, but they are at greater risk for dangerous clots.

An estimated one in 100 women experiences three or more consecutive miscarriages, which has been linked to a number of factors, including the woman’s age, chromosome abnormalities carried by her or the father, abnormalities in the embryo, structural problems in the womb, infections, and certain blood conditions, including thrombophilia.

Thrombophilia can cause a blood clot in the placenta leading to miscarriage, so women with a genetic susceptibility to thrombophilia are often given blood thinners during pregnancy to reduce that risk.

Dr. Lund and her colleagues wanted to know if women with repeated miscarriages and either of two particular genetic mutations associated with thrombophilia were more likely to miscarry again, since previous research had produced conflicting conclusions.

They looked at the medical records and pregnancies of 363 Danish women who had experienced recurrent pregnancy loss. Thirty-five (9.7 percent) of the women tested positive for one of the two most common thrombophilia-related mutations.

In the entire group, there were 224 live births, five still-births, 133 miscarriages and one early termination of pregnancy due to chromosomal abnormalities. The live birth rate was higher for women without the mutations (63.4 percent) than for women with the mutations (45.7 percent).

When other factors, such as the mother’s age, smoking status, and previous number of miscarriages, were taken into account, however, the differences in live birth rates between mutation-positive and mutation-negative women were “found to be strong but not statistically significant,” Lund said.

Such a thorough analysis of pregnancy outcomes in women with and without the thrombophilia-associated mutations had not been conducted before, the authors note in the October 11 issue of the journal Human Reproduction.

The only difference of significance was in the rate of excessive bleeding at delivery, which was higher for the mutation-positive women.

Finding excessive bleeding among the mutation carriers has implications for what is now a standard practice of prescribing blood thinning treatments to thrombophilia-mutation carriers and sometimes to women without known mutations who have experienced three or more miscarriages.

The evidence, the authors write, does “not support anticoagulation therapy” for women with unexplained miscarriages but does suggest the need for more well designed clinical trials to investigate further.

SOURCE:  Human Reproduction, online Oct. 11, 2010.

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