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Anticoagulants and pregnancy: When are they safe?

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References

Other issues with warfarin are the effect of variations in dietary vitamin K intake on anticoagulation and potential drug interactions that may alter the anticoagulant effect. Thus, the INR needs to be monitored closely.

Risks to the fetus and the mother

Unlike the heparins, coumarins freely cross the placenta and thus pose a risk of teratogenicity. A cluster of fetal malformations including “warfarin embryopathy” (nasal bone hypoplasia and chondrodysplasia punctata) can occur when the drug is used between 6 and 12 weeks of gestation. Warfarin embryopathy may be avoided by stopping warfarin prior to 6 weeks from the onset of the last menstrual period (ie, 6-week “menstrual age” or 4-week gestational age 34).

Later in pregnancy, warfarin is associated with potential fetal bleeding complications leading to central nervous system abnormalities, increased rates of intrauterine fetal death, and pregnancy loss. In pregnant women with mechanical cardiac valve prostheses who received oral anticoagulants throughout pregnancy, the incidence of congenital anomalies was 6.4% to 10.2%. 35 Fetal demise (spontaneous abortion, stillbirth, neonatal death) was also very common (29.7% to 33.6% of pregnancies) in coumarin-treated women.

Severe maternal hemorrhage may also occur in pregnant women on oral anticoagulants, particularly those who remain fully anticoagulated around the time of labor and delivery.

General caveats to warfarin in pregnancy

Because of the many maternal and fetal concerns, oral anticoagulant use in pregnancy is largely restricted to women with older-generation prosthetic heart valves in whom the very high maternal thrombotic risk may outweigh the risk of maternal and fetal side effects.

While there are limited data on warfarin use in pregnant women with antiphospholipid syndrome, 36 warfarin use in such patients should be considered only for those at highest risk and with careful informed consent. These issues are discussed further below in the section on mechanical heart valve prostheses.

ANTIPLATELET DRUGS

Aspirin is an antiplatelet agent rather than an anticoagulant. Although considered inadequate for preventing venous thrombosis in high-risk groups when used alone, aspirin can moderately reduce the risk of deep venous thrombosis and pulmonary embolism in nonpregnant patients. 37 It also has a well-accepted role in preventing arterial thrombotic events, ie, coronary artery disease and stroke. 38

Low-dose aspirin (≤ 100 mg/day) has been extensively evaluated during pregnancy 39–41 and has been shown to be safe and effective in reducing the risk of preeclampsia in high-risk women 39 and in treating women with antiphospholipid antibodies and recurrent pregnancy loss 42 (in conjunction with prophylactic doses of heparin). Although higher doses of aspirin and other nonsteroidal anti-inflammatory drugs can be toxic to the fetus, low doses have been shown to be safe throughout pregnancy. 43

Dipyridamole (Persantine) has been studied extensively in pregnancy, and while it appears to be safe, it has not found a well-defined therapeutic role.

Other antiplatelet drugs have been only rarely used, and data on their safety and efficacy during pregnancy are limited to case reports, for example, on ticlopidine 44 (Ticlid) and clopidogrel 45,46 (Plavix) given during pregnancy in women with cardiac disease. These drugs do not appear to be major teratogens or to cause specific fetal harm. Their use may be reasonable in some high-risk situations, such as recurrent thrombotic stroke despite aspirin therapy. They may be used alone or with other anticoagulants in women with a coronary or other vascular stent if fetal safety is uncertain or if there is an increased risk of maternal bleeding.

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