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Anticoagulants and pregnancy: When are they safe?

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Options for women requiring ongoing therapeutic anticoagulation include intravenous heparin started without a bolus, to minimize bleeding risk, with aPTT measured 12 hours later, or an initial prophylactic dose of LMWH 6 to 12 hours postpartum, with therapeutic dosing resumed on postpartum day 1. If prophylactic dosing is desired, unfractionated heparin or LMWH may be given subcutaneously starting at about 6 hours postpartum.

Warfarin in the puerperium

Women may subsequently be maintained on either LMWH or unfractionated heparin, or switched to an oral anticoagulant such as warfarin. Although warfarin may appear in minute amounts in breast milk, it has not been associated with adverse events in newborns and is considered compatible with breastfeeding. 68 Heparin should be continued during the initial days of warfarin therapy, until the INR is at a therapeutic level for 24 hours. Some physicians prefer to delay warfarin for several days, giving LMWH alone in the immediate postpartum period, to allow wound-healing and to reduce bleeding risk.

Postpartum, anticoagulation should be continued for at least 6 to 12 weeks, at which point the physiologic changes in the coagulation system related to pregnancy will have returned to normal.

THROMBOPHILIA WITHOUT A PREVIOUS THROMBOEMBOLIC EVENT

Over the last 5 to 10 years, practitioners have been seeing many more young women with genetic or acquired thrombophilias who have never had a venous thromboembolic event. Physicians must advise these women about their risk of thromboembolic events during pregnancy and about the appropriateness of anticoagulant use.

Thrombophilias are often detected in women who develop venous thrombosis during pregnancy, 69–71 but they are also very common in the general population (around 15%). While women with thrombophilia are at above-average risk of venous thromboembolism during pregnancy, the magnitude of risk in an individual patient is often difficult to estimate.

Data suggest that some types of thrombophilia confer greater thrombotic risk than others. McColl et al 72 derived risk estimates for a primary event in women with several of the disorders: 0.23% in women heterozygous for the factor V Leiden mutation, 0.88% in women with protein C deficiency, and 2.4% to 35.7% in women with antithrombin deficiency. A case-control study 70 found that all thrombophilic states were more common in women with pregnancy-associated venous thromboembolism than in healthy pregnant controls, except those with the MTHFR mutation and protein S deficiency. The estimated risk during pregnancy was 0.03% in women with no defect, 0.1% in women with protein C deficiency, 0.25% in women with the factor V Leiden mutation, 0.4% in those with antithrombin deficiency, 0.5% in those with the prothrombin gene mutation, and 4.6% in those with both factor V Leiden and prothrombin gene mutations.

Routine anticoagulation not advised in pregnant thrombophilic women

Because the risk of a primary venous thromboembolic event is less than 1% for most thrombophilic women, routine anticoagulant therapy does not seem prudent for this indication. Given the low absolute risk of venous thromboembolism, the cost and potential side effects of anticoagulant use are difficult to justify.

The women who seem at higher risk and in whom anticoagulation should be considered include those with antithrombin deficiency; those with high-titer anticardiolipin antibodies or a lupus anticoagulant antibody (treat with heparin and low-dose aspirin); those with combined thrombophilic defects or who are homozygotes for the factor V Leiden or prothrombin gene mutations; and those with multiple other current risk factors for venous thromboembolism ( Table 1 ).

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