Challenges of Anticoagulation Therapy in Pregnancy

Thrombotic complications in pregnancy represent a major cause of morbidity and mortality. Pregnancy is a primary hypercoagulable state due to enhanced production of clotting factors, a decrease in protein S activity, and inhibition of fibrinolysis. These physiologic changes will yield a collective rate of venous thromboembolism (VTE) of about 1–2 in 1000 pregnancies for the general obstetric population, which represents a five- to tenfold increased risk in pregnancy compared to age-matched non-pregnant peers. A select group of women, however, will carry a significantly higher rate of thrombosis due to primary thrombophilia, either inherited or acquired. This introduces a population of women who may benefit from prophylactic anticoagulation, either antepartum or postpartum. The coagulation changes that occur in preparation for the hemostatic challenges of delivery endure for several weeks postpartum. In fact, daily risk for pulmonary embolism (PE) is the highest postpartum. Use of anticoagulation in pregnancy introduces particular risk at the time of delivery, where bleeding and clotting risk collide. Altered metabolism rates of anticoagulants in pregnant women often necessitate closer monitoring than is required outside of pregnancy in order to ensure efficacy and safety. Heparin products are the mainstay of treating VTE in pregnancy, chiefly because they do not cross the placenta. In women with mechanical heart valves, the ideal anticoagulation regimen remains controversial as heparin use has shown inferior outcomes for preventing thromboembolic complications compared to warfarin, but warfarin carries risk for fetal embryopathy. Other populations where a heparin alternative is necessary include women with a history of heparin-associated thrombocytopenia (HIT) or other heparin intolerance. Further challenging the management of anticoagulation in pregnancy is the dearth of randomized clinical trials. The evidence governing treatment recommendations is largely based on expert guidelines, observational studies, or extrapolation from non-pregnant cohorts. A careful critique of a woman’s history, as well as the available data, is essential for optimal management of anticoagulation in pregnancy. Such decisions should involve a multidisciplinary team involving obstetrics, hematology, cardiology, and anesthesia.