A patient is on life-long warfarin and wishes to become pregnant. How should she be managed?

All anticoagulant options during pregnancy are associated with potential risks to the mother and fetus. Any woman on warfarin who wishes to become pregnant should ideally be seen for prepregnancy counselling and should be involved in the anticoagulation decision as much as possible. Potential risks to the fetus need to be balanced against the increased maternal thrombotic risk during pregnancy. Anticoagulation for mechanical heart valves in pregnancy remains an area of some controversy.

The use of warfarin during pregnancy is associated with a low risk of maternal complications1 but it readily crosses the placenta and embryopathy can follow exposure between 6–12 weeks’ gestation, the true incidence of which is unknown. A single study has reported that a maternal warfarin dose 5mg is without this embryopathy risk.2 As pregnancy progresses, the immature vitamin K metabolism of the fetus can result in intracranial haemorrhage even when the maternal INR is well controlled. In addition, a direct CNS effect of warfarin has been described, resulting in structural abnormalities. Conversion to heparin in the final few weeks of pregnancy is recommended to prevent the delivery of, what is in effect, an anticoagulated fetus.

In contrast, unfractionated heparin (UFH) is free from direct fetal harm but it has varied pharmacokinetic and anticoagulant effects and adequate maternal anticoagulation can be difficult to achieve. The use of UFH in women with mechanical valve replacements during pregnancy has been associated with increased maternal thrombosis and bleeding. Studies have been criticised for the use of inadequate heparin dosing and/or inadequate therapeutic ranges although a recent prospective study which used heparin in the first trimester and in the final weeks of pregnancy reported fatal valve thromboses despite adequate anticoagulation. Long term heparin use risks osteoporosis and heparin-induced thrombocytopenia (HIT). Intensive monitoring is required in pregnancy and the use of anti-Xa assays may be necessary.

Low molecular weight heparins (LMWH) have a more reliable anticoagulant effect.6 The dose is adjusted according to anti-Xa levels. Use in pregnancy is mainly for thromboprophylaxis rather than full anticoagulation but experience is increasing. Indeed, case reports are starting to emerge where LMWH has been used for mechanical valve replacements. Compared with UFH the risk of HIT and osteoporosis are reduced6 and these heparins may hold the future for anticoagulation in pregnancy.

Management
Women who do not wish to continue warfarin throughout pregnancy can be reassured that conceiving on warfarin appears safe but conversion to heparin, to avoid the risk of embryopathy, needs to be carried out by 6 weeks. Breast-feeding on either warfarin or heparin is safe. Possible regimes include:

• Warfarin throughout pregnancy until near term and then conversion to unfractionated heparin.
• Unfractionated heparin for the first trimester. Warfarin until near term and then resumption of heparin.