Antithrombotic therapy in pregnancy

Antithrombotic therapy in pregnancy - technical

Antithrombotic therapy in pregnancy is limited essentially to warfarin and heparin. There are insufficient data on newer antiocoagulants such as recombinant hirudin and fondaparinux to allow recommendations in pregnancy. Low dose aspirin is not associated with adverse pregnancy outcome in the second and third trimesters and may be useful in some situations, either alone or combined with low molecular weight heparin (LMWH) such as in antiphospholipid syndrome.

Warfarin

The use of warfarin in pregnancy is restricted to only a few situations where heparin is considered unsuitable. Although warfarin is not secreted in breast milk in significant amounts and is safe to use during lactation, it crosses the placenta and is teratogenic with around 6% of pregnancies exposed being associated with congenital abnormalities. With exposure between 6 and 9 weeks’ gestation warfarin embryopathy (midface hypoplasia, stippled chondral calcification, scoliosis, short proximal limbs, and short phalanges) may occurs with estimates varying from 0.6 to 5%. This problem is potentially preventable by substitution of heparin for warfarin during the first trimester.

Prenatal exposure to coumarins is also associated with an increased risk of neurodevelopmental problems. Warfarin should be avoided around the time of delivery because of maternal and fetal bleeding risk, and hence if used in pregnancy is usually stopped at around 36 weeks gestation (see: Heart disease in pregnancy).

Heparin

Neither unfractionated heparin (UFH) nor LMWH appears to cross the placenta and there is no evidence of teratogenesis or risk of fetal haemorrhage. Heparins are not secreted in breast milk and can be used during breastfeeding.

Prolonged use of UFH is associated with symptomatic osteoporosis, with a 2% incidence of osteoporotic fractures. Allergy and heparin-induced thrombocytopenia, an antibody-mediated effect that leads to arterial and venous thrombosis due to platelet activation, may occur.

LMWHs appear safe for the mother and fetus, with a substantially lower risk of osteoporosis and a negligible risk of heparin-induced thrombocytopenia compared to UFH, but local allergic reactions (itchy, erythematous lesions at the injection sites) can occur as with UFH. Changing the heparin preparation may be helpful, but cross-reactivity is common. Skin reactions can be associated with heparin-induced thrombocytopenia, hence the platelet count should be checked if these develop.

The risk of recurrent venous thrombosis with LMWH used for thromboprophylaxis in pregnancy is less than 1%. LMWHs are not associated with an increased risk of severe peripartum bleeding, hence LMWH is now the anticoagulant of choice in pregnancy because of a better side effect profile, good safety record for mother and fetus, and convenient once-daily dosing for prophylaxis.

Graduated elastic compression stockings

In view of the pregnancy-related changes in the venous system, graduated elastic compression stockings should be of value in pregnancy and postpartum. Full-length stockings are usually used in pregnancy where ileofemoral thrombosis is more common, and indeed they are recommended in high-risk situations for prophylaxis, but most data on efficacy in nonpregnant women come from below-knee stockings, which patients may be more likely to wear.

Antiembolism stockings for prophylaxis have a pressure of around 20 mmHg at the ankle, but graduated elastic compression stocking with an ankle pressure of 30 to 40 mmHg should be used after a deep venous thromboses. Long-term use after deep venous thromboses may reduce the risk of post-thrombotic syndrome.

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Thromboprophylaxis in pregnancy

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