I am Factor V Leiden, homozygous. I have had a successful pregnancy, although I spent two months of it in the hospital. My son (heterozygous) is now eight months old and growing well. My sister is heterozygous. She is now six weeks pregnant. The doctors said she had a bigger placenta than normal. They are waiting for a week to hear the baby's heartbeat. They are worried that the baby could not develop enough, and they are talking about terminating the pregnancy. Can the Factor V Leiden abnormality be responsible for this? If so, why would she develop this problem and not me?

R.S.

The Factor V Leiden mutation is a particular variant of the gene governing the blood-clotting component known as Factor V. "Homozygous" means you inherited two genes for this variant -- one from your mother and one from your father. Your sister, who is heterozygous, inherited one gene for the condition, and one gene that does not have the mutation.

In the May 1999 issue of the Annals of Internal Medicine, Dr. Johan Meinardi reported an increased risk of pregnancy loss in both those who are homozygous or heterozygous carriers of the Factor V Leiden mutation. Fetal loss of any type occurred in 31.6 percent of carriers (compared with 22.3 percent of noncarriers). Miscarriage -- meaning fetal loss in the first 20 weeks of pregnancy -- occurred in 29.4 percent of carriers (17.4 percent in noncarriers). Stillbirth -- meaning fetal loss after 20 weeks of pregnancy -- occurred in 5.7 percent of carriers (5.0 percent in noncarriers). Fetal loss recurred in 10.1 percent of carriers (4.1 percent in noncarriers). Homozygous carriers had a greater risk for fetal loss and stillbirth than heterozygous carriers.

One cause of pregnancy loss is clotting in the small blood vessels of the placenta. The placenta carries out a complex role, exchanging nutrients between the mother and the fetus at the same it serves as a barrier keeping the fetal and maternal blood supply separate. As clotting can occur on either the fetal or the maternal side of the placenta, we need to ask whether the increased risk of placental clotting and fetal loss is based a problem in the mother's blood or the fetus's. The importance of this distinction is heightened by the fact that the frequency of the factor V Leiden mutation in miscarried fetuses has been found to be more than twice that in the general population. Thus it appears that the carrier status of the fetus, rather than that of the mother, may be the main consideration in fetal loss.

This finding could have significant implications in treatment of women with this condition. The drug heparin, which reduces clotting, is commonly prescribed to prevent pregnancy loss in women who carry the Factor V Leiden mutation. However, as heparin does not cross the placenta, it may be less effective or ineffective at preventing pregnancy loss if the cause of the problem lies with the fetus' blood, rather than the mother's.

In any case, I do not believe that this condition would result in an enlarged placenta. Nor do I believe that your sister would likely benefit from pregnancy termination unless there is some other problem of which we are not aware.