Options of Anticoagulant Therapy During Pregnancy: Focus on Fondaparinux
The use of most medicinal products is limited during pregnancy either by known teratogenic effects or by lack of safety data for the mother and fetus. A systematic review by authors from the University of Liverpool provides information on the options for anticoagulant treatment during pregnancy.
Anticoagulant Therapy During Pregnancy
Pregnancy is known to be a physiological pro-coagulant state. Anticoagulant therapy is indicated if the pregnant woman's history indicates an increased risk of thromboembolic disease or if thrombosis or embolism is diagnosed during pregnancy.
The drug of choice is currently low molecular weight heparin, which does not cross the placental barrier and is safe for the fetus. However, some patients may develop heparin-induced thrombocytopenia or experience skin reactions or osteopenia while using it. In these cases, a change of anticoagulant therapy is indicated.
Use of Fondaparinux
The authors of the presented review evaluated available data on the use of newer anticoagulants during pregnancy. After evaluating 561 citations, 11 articles were included in the review: 10 on fondaparinux (a total of 24 cases of women using fondaparinux during pregnancy) and 1 on ximelagatran (which has been withdrawn from the market due to its hepatotoxicity). Fondaparinux is a selective factor Xa inhibitor; unlike rivaroxaban, apixaban, and edoxaban, it is administered subcutaneously.
Seven articles described the use of fondaparinux for the prophylaxis of thromboembolic disease in women who had previous skin reactions to heparin or low molecular weight heparin. The typically used prophylactic dose was 2.5 mg daily. In 2 patients, blood loss greater than 1000 ml was described during childbirth, but blood transfusion was not indicated. Other bleeding complications were not reported. In one case, an acute cesarean section was indicated at 34 weeks of gestation due to intrauterine growth retardation (IUGR). However, this woman had a history of systemic lupus erythematosus associated with antiphospholipid syndrome, which may be the cause of IUGR.
Three articles dealt with the use of fondaparinux in treating thromboembolic disease developing during pregnancy. The standard therapeutic dose was 7.5 mg daily. In all three cases, fondaparinux was discontinued 24 hours before the use of regional anesthesia, and no pregnancy complications or effects on fetal development were described.
Other Anticoagulants
Warfarin is contraindicated during pregnancy due to its known teratogenic effects. The use of new (direct) oral anticoagulants (NOACs) is not recommended during pregnancy due to a lack of safety data for the mother and fetus.
Conclusion
From limited experiences with the use of fondaparinux during pregnancy, it can be considered safe and may be an alternative for the prophylaxis and treatment of thromboembolic disease when heparin or low molecular weight heparin cannot be used.
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Source: Tang A.-W., Greer I. A systematic review on the use of new anticoagulants in pregnancy. Obstet Med 2013; 6 (2): 64–71, doi: 10.1177/1753495x12472642.
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