Vol. 20: Fall 2002
Genetic Considerations in Thrombotic Disorders
Teratogen Hot Topic: Anticoagulants
The use of some anticoagulants during pregnancy can carry a slightly increased risk to the developing embryo and fetus. The list of anticoagulants presented here is not exhaustive, but represents those commonly used to treat thrombotic disorders.
Warfarin (also called coumarin derivatives) has been associated with underdevelopment of the nose, stippling of the ends of the long bones and, possibly, developmental delay. The nose grows in length, width as well as away from the face. It is the growth away from the face that can be affected by warfarin, leaving the nose flat against the face. A flatness that, in some cases, can impair breathing and require some reconstructive surgery. Warfarin can also cause stippling at the ends of the long bones (the epiphyses). This stippling shows up on radiographic examination, but has no clinical significance. These effects of warfarin on the nose and long bones are seen with embryonic exposure between weeks 6 and 9 and occur in less than 10% of those exposed. Warfarin has also been associated, very weakly, with a possible increase in developmental delay. This finding has not been substantiated across studies as have the other teratogenic effects of the drug and is, therefore, still in question. If there is an effect on brain development, the risk is very low and the gestational time at which warfarin may induce this finding in the fetus is not known.
Heparin has a very large molecular weight and is one of only a few drugs that do not cross the placenta. Because of its size, heparin is considered the treatment of choice for clotting disorders during pregnancy.
Low molecular weight, oral dosing forms of heparin are now available for use. These forms of heparin are being closely monitored when used by pregnant women, and, so far, no increased risks for birth defects have been reported. These drugs are used only if patients are unable to use regular heparin.
Low dose aspirin (usually 80mg/day) has not been associated with an increased risk to the fetus when used by pregnant women. Aspirin used in regular doses after 26 weeks of pregnancy is sometimes associated with premature closure of the ductus arteriosus, a vessel in the fetal heart. Closure can lead to fetal pulmonary hypertension causing prematurity and, rarely, stillbirth. This effect has not been seen with the low doses of aspirin used to control clotting. However, when pregnant women are treated with aspirin, even in low doses, after 30 weeks gestation, many obstetricians monitor for ductal closure on a regular basis, just to be cautious.
All anticoagulants, of course, carry concern for maternal bleeding during labor and delivery. Discontinuation of therapy near term is done, if possible. The length of time before the mother’s due date that therapy is discontinued is dependent upon many variables and decisions about timing are made on a case-by-case basis.
Contributed by Lynn Martinez (UT)
Genetic Considerations in Thrombotic Disorders
Table of Contents
Introduction
Adult Thrombotic Disorders
Pediatric Thrombotic Disorders
Fetal and Neonatal Effects of Maternal/Fetal Thrombotic Disorders
Teratogen Hot Topic: Anticoagulants
Heterozygote Counseling for Factor V Leiden mutation
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