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Anticoagulants and pregnancy: When are they safe?

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LMWHs, on the other hand, interact relatively little with factor II and do not predictably prolong the aPTT. Monitoring their effect is therefore more difficult and requires direct measurement of anti-factor-Xa activity. This test is widely available, but it is time-consuming (it takes several hours and results may not be available within 24 hours if the test is requested “after hours”), and therefore it is of limited use in the acute clinical setting. While weight-based dosing of LMWHs is reliable and safe in nonpregnant patients, it has not yet been validated for pregnant women.

Unfractionated heparin has been used for decades for many indications during pregnancy. It is a large molecule, so it does not cross the placenta and thus, in contrast to the coumarin derivatives, does not cause teratogenesis or toxic fetal effects. Its main limitations in pregnancy are its inconvenient dosing (at least twice daily when given subcutaneously) and its potential maternal adverse effects (mainly osteoporosis and heparin-induced thrombocytopenia).

Over the last 10 years LMWHs have become the preferred anticoagulants for treating and preventing thromboembolism in all patients. They are equivalent or superior to unfractionated heparin in efficacy and safety in the initial treatment of acute deep venous thrombosis 9,10 and pulmonary embolism 11,12 outside of pregnancy. While comparative data are much less robust in pregnant patients, several series have confirmed the safety and efficacy of LMWHs in pregnancy. 13–15 LMWHs do not cross the placenta 15–17 and thus have a fetal safety profile equivalent to that of unfractionated heparin.

Pregnancy alters metabolism of LMWHs

The physiologic changes of pregnancy alter the metabolism of LMWH, resulting in lower peak levels and a higher rate of clearance, 18,19 and so a pregnant woman may need higher doses or more frequent dosing.

Recent evidence suggests that thromboprophylaxis can be done with lower, fixed, once-daily doses of LMWH throughout pregnancy, 20 although some clinicians still prefer twice-daily dosing (particularly during the latter half of pregnancy).

For therapeutic anticoagulation, however, the dose of LMWH required to achieve the desired level of anti-factor-Xa activity appears to change significantly over the course of pregnancy in many women. 18 Therapeutic dosing of LMWH may also require twice-daily dosing, depending on the agent used ( Table 2 ).

Pending more research on weight-based dosing of LMWH in pregnancy, anti-factor- Xa activity levels should be measured after treatment is started and every 1 to 3 months thereafter during pregnancy. 21 Doses should be adjusted to keep the peak anti-Xa level (ie, 4 hours after the dose) at 0.5 to 1.2 U/mL. 22

Heparin-induced thrombocytopenia

Type-2 heparin-induced thrombocytopenia is an uncommon but serious adverse effect of unfractionated heparin therapy (and, less commonly of LMWH), caused by heparin-dependent immunoglobulin G (IgG) antibodies that activate platelets via their Fc receptors, potentially precipitating life-threatening arterial or venous thrombosis.

In a trial in nonpregnant orthopedic patients, 23 clinical heparin-induced thrombocytopenia occurred in 2.7% of patients receiving unfractionated heparin vs 0% of those receiving LMWH; heparin-dependent IgG was present in 7.8% vs 2.2%, respectively.

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