title: The "warfarin window" in pregnancy: the importance of half-life.
abstract: 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.
authors.affiliation: Motherisk Program, Hospital for Sick Children, Toronto ON.
authors.forename: Asnat
authors.initials: A
authors.lastname: Walfisch
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology; D002356:Cartilage / Q000187:drug effects / Q000196:embryology; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced*; D005865:Gestational Age; D006207:Half-Life; D006350:Heart Valve Prosthesis; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006493:Heparin