The "warfarin window" in pregnancy: the importance of half-life.

Anticoagulation therapy during pregnancy in women with prosthetic cardiac valves is a therapeutic challenge. The use of vitamin K antagonists such as warfarin during pregnancy carries the potential for serious risks to the fetus, especially if these drugs are administered during the first trimester or at term. Between 6 and 12 weeks' gestation, fetal synthesis of proteins crucial for bone and cartilage formation may be impaired by warfarin, resulting in the well-defined "warfarin embryopathy." One of the most commonly suggested regimens involves the substitution of heparin for warfarin between 6 and 12 weeks' gestation to minimize the risk of warfarin embryopathy. Warfarin has a long half-life; following a single dose, the terminal elimination half-life is about one week, with a mean effective half-life of 40 hours. To date, all existing guidelines have ignored this long elimination half-life. If a policy of substituting heparin for warfarin between 6 and 12 weeks' gestation is followed, we suggest that substitution should begin at a much earlier gestational age. Substitution starting at 6 weeks' gestation may be too late to avoid embryopathy.