USE OF WARFARIN IN PREGNANCY

Warfarin is a coumarin anticoagulant and vitamin K antagonist which acts by inhibiting clotting factors II, VII, IX and X. It is indicated for: the prevention of systemic embolism in patients with rheumatic heart disease and atrial fibrillation, prophylaxis after insertion of prosthetic heart valves, prophylaxis and treatment of venous thrombosis and pulmonary embolism, and treatment of transient cerebral ischaemic attacks.

Fetal warfarin syndrome (FWS) or warfarin embryopathy, characterised by nasal hypoplasia and skeletal abnormalities, including short limbs and digits, and stippled epiphyses, is a well-recognised complication of first trimester warfarin use in pregnancy. The critical risk period for FWS is thought to span gestational weeks 6-12, but has not been definitively confirmed. The likelihood of warfarin embryopathy following exposure during this critical period has been proposed to be as high as 30%, although more recent studies suggest a risk of 6-10%. There is some evidence that the risk of FWS may be dose-dependent, with doses of >5mg carrying a higher risk, although doses less than this are not without risk.

Exposure that extends beyond or commences after the first trimester of pregnancy has been associated with CNS defects and eye anomalies. Second and third trimester exposure confers a risk of fetal, placental or neonatal haemorrhage.

Postnatal developmental delay has been observed following in utero exposure to warfarin, but when reported was mainly in children with FWS.

Use of warfarin in pregnancy may be associated with an increased incidence of spontaneous abortion and stillbirth; this has also been reported following use of other anticoagulants such as heparin.

Warfarin exposure in pregnancy should be avoided if possible by changing to a non-teratogenic anticoagulant, usually a low molecular weight heparin (LMWH), before pregnancy or as soon as possible after pregnancy is suspected. In some patients with mechanical heart valves the continued use of warfarin may need to be considered where other agents do not provide adequate anticoagulation.

Detailed ultrasound scans should be considered to screen for structural anomalies associated with fetal warfarin syndrome where exposure has occurred during or beyond the first trimester. Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.