Abnormal Clotting Protein Predicts Miscarriage Risk
Women with history of problem could be screened, study says
TUESDAY, Jan. 29, 2002 (HealthDayNews) -- A relatively common gene mutation that promotes blood clots in both pregnant women and placentas strongly predicts miscarriage and stillbirth, English researchers say.
Scientists in London found women with an anomaly in a protein called Factor V and a history of pregnancy trouble were much more likely to miscarry than those without the mutation were. The flaw is also linked to a higher risk of stillbirth.
Dr. Raj Rai, a reproductive medicine specialist at Imperial College and leader of the study, cautions the results don't suggest every pregnant woman be screened for the protein. However, he says, the work should encourage genetic testing in women with a history of early miscarriages, as well as those with even a single late miscarriage or stillborn delivery.
Should the test prove positive, doctors may be able to use blood thinners -- particularly heparin -- to prevent clot-related complications, says Rai, whose findings appear in tomorrow's issue of the journal Human Reproduction. However, experts say that strategy is still experimental and hasn't been shown to reduce the risk of lost pregnancies.
Roughly 5 percent of white women have the mutation, called Factor V Leiden (FVL), far more than among blacks or Asians, experts say. The mutation boosts the odds of having blood clots fourfold over other women, a risk that rises to a factor of 10 for those who also take birth control pills. The mutation also has been linked to strokes.
Even women without the abnormal clotting protein are vulnerable to clotting when they're pregnant. During gestation, their blood thickens to protect the placenta from shearing away from the womb.
Miscarriages occur in between 10 percent and 25 percent of pregnancies, or possibly even more, depending on how they're counted. Most are believed to result from chromosomal anomalies. Yet researchers have suspected clotting problems may lurk behind a substantial share of repeat miscarriages in the first three months of gestation, as well as fetal deaths in subsequent trimesters, when the risk of such problems falls off dramatically.
To test this hypothesis, Rai and his colleagues studied 25 women with one FVL mutation (having two bad copies is extremely rare) and three or more miscarriages before or around 12 weeks. They also included women who'd lost at least one pregnancy after that cutoff, and a control group of women with similar pregnancy histories but normal FVL.
Women with the gene flaw and recurrent early miscarriages were 3.75 times less likely to have a live birth than those with the normal clotting protein. In addition, only one of the nine women with a pattern of late miscarriage and FVL had a live birth, versus 22 of the 45 women with the normal protein.
"This study tells us that these women, when followed prospectively, had outcomes that were certainly less [desirable] than those who did not have this abnormality," says Dr. Mark Perloe, an Atlanta fertility specialist. "This doesn't necessarily mean that we should go out and screen all people, nor does it prove that treatment will reduce the likelihood of miscarriage. That's really the next step."
Perloe notes that many clinics in the United States, including his own, screen for FVL in women with a history of miscarriages. Many also offer blood thinners to those with the mutation. However, it would be nice to know whether that therapy helps prevent pregnancy loss, he says.
Rai says he and his colleagues are now conducting a trial to see if heparin does just that.
"Heparin doesn't cross the placenta, so the baby's never exposed to it," he says. The drug is fairly safe for the mother, and new evidence shows it doesn't accelerate the normal process of bone loss during pregnancy, as previously feared, he adds.
Dr. D. Ware Branch, a women's health expert at the University of Utah in Salt Lake City, calls the latest work "a very important" contribution to the understanding of clotting and pregnancy loss. Mutant FVL and flaws in another blood protein, prothrombin, appear in 7 percent to 8 percent of women in Utah, and more in Western Europe, Branch says.
"It is reasonable to assume that there really are a host of other clotting abnormalities, and as a group all of them may be a relatively common contributor to stillbirth, early fetal death" and embryo loss, Branch says.
Why so many white women have the FVL mutation is intriguing, especially considering how much trouble it can cause during pregnancy, Branch says.
"It may be that there are advantages to this mutation at some point in our lives, whether it be early or later on, including those associated with bleeding at delivery," he says.
So far, he says there's no evidence for that speculation. However, some research hints that women with the mutation may have more success at receiving embryos through in vitro fertilization procedures, Ware says. The significance of that finding isn't yet clear.
What To Do
To find out more about Factor V Leiden, try the University of Pittsburgh.
You can also check out this site devoted to the mutation.
For more on miscarriages, visit this Women's Health Information web site from Britain.