Anticoagulants and pregnancy: When are they safe?

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For women on indefinite therapeutic anticoagulation (ie, because of recurrent thrombosis), full therapeutic anticoagulation with LMWH or adjusted-dose unfractionated heparin should be maintained throughout pregnancy, as described above.

Which other women should receive prophylactic anticoagulation is a topic of ongoing debate and controversy.

How great is the risk of recurrent thromboembolism?

A small observational study 59 examined the risk of recurrent venous thromboembolism during subsequent pregnancies in women with a prior thrombotic event. Anticoagulation was withheld during the antepartum period and restarted briefly after delivery. Among the 125 women enrolled, recurrent venous thromboembolism occurred in 4.8%, with half of the events occurring during the antepartum period. Among those with underlying thrombophilia, the rate of recurrent venous thromboembolism was 13% (95% confidence interval [CI] 1.7%–40.5%) to 20% (95% CI 2.5%–56.5%), and those with a prior idiopathic clot without thrombophilia had an event rate of 7.7% (95% CI 0.01%–25.1%). The subgroup with a prior reversible risk factor (at the time of their initial venous thromboembolic event) and without detectable thrombophilia had no recurrent events.

This study suggests that women with prior venous thromboembolism and thrombophilia or a prior idiopathic thrombotic event are at a substantial risk of recurrent thrombotic events during pregnancy. And other data confirm the high risk of recurrent venous thromboembolism in thrombophilic pregnant women. 60 These women should all be offered active antepartum and postpartum thromboprophylaxis with LMWH or unfractionated heparin ( Tables 2 and 4 ). Women without thrombophilia but with a history of venous thromboembolism related to pregnancy or oral contraceptive use also have a substantial risk of recurrent venous thrombosis and should be offered antepartum and postpartum thromboprophylaxis. 61 In contrast, women with a prior “secondary” clot, no thrombophilia, and no additional current risk factors ( Table 1 ) appear to be at low risk of recurrent venous thromboembolism.

The risks should be discussed with these women, with an option for close clinical surveillance during pregnancy ( Table 4 ), but with a low threshold to investigate any worrisome symptoms. Such women may also elect to take LMWH or unfractionated heparin during pregnancy.

Which heparin to use?

Prophylactic anticoagulation during pregnancy can be with either LMWH or unfractionated heparin. For most women this involves “prophylactic” dosing with the goal of maintaining a mid-interval anti-factor-Xa activity level of approximately 0.05 to 0.2 U/mL. Thromboprophylaxis with LMWH can be with lower, fixed, once-daily doses throughout pregnancy 20 ( Table 2 ), although some clinicians still prefer twice-daily dosing. The heparin should be started as soon as pregnancy is confirmed, as the pregnancy-associated increase in thrombotic risk begins by the middle of the first trimester.

To maintain effective prophylactic levels, the dose of unfractionated heparin should be increased sequentially over the trimesters 62,63: approximately 5,000 units subcutaneously twice daily in the first trimester, then 7,500 units twice daily in the second trimester, and 10,000 units twice daily in the third trimester for a woman of average size.

When to add low-dose aspirin

Women with antiphospholipid antibodies, particularly those with prior recurrent pregnancy loss or fetal demise, should receive aspirin 81 mg/day in addition to heparin. 39 The aspirin may be started prior to conception or when pregnancy is confirmed.

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