Bayer Pharma AG

Safety of anticoagulation during pregnancy

Safety of anticoagulation during pregnancy

A risk of bleeding can be associated with any anticoagulation therapy; however, in pregnant patients, other safety concerns may also need to be considered. The use of unfractionated heparin (UFH) during pregnancy is associated with reduced bone density, vertebral fracture and a small risk of heparin-induced thrombocytopenia (HIT). Low molecular weight heparin (LMWH) use for the treatment or prevention of acute venous thromboembolism (VTE) during pregnancy is associated with adverse events including arterial thrombosis, osteoporosis, bleeding and allergic skin reactions. Adverse events such as HIT, bleeding and osteoporosis have been shown to occur at a lower frequency in patients receiving LMWHs compared with those receiving UFH. Vitamin K antagonists (VKAs) are not recommended during pregnancy.

Guideline Recommendations

The American College of Chest Physicians (ACCP) guidelines recommend thromboprophylaxis with low molecular weight heparin (LMWH) for the prevention of venous thromboembolism (VTE) in pregnant women with a history of VTE and a moderate-to-high risk of recurrence. Thromboprophylaxis is not recommended in certain cases. Vitamin K antagonist (VKA) use is not recommended during pregnancy, but the use of warfarin and acenocoumarol are options after childbirth. The use of fondaparinux and parenteral direct thrombin inhibitors should be limited to women with severe allergic reactions to heparin. Novel oral agents, such as dabigatran, rivaroxaban, apixaban and edoxaban, are not recommended in current guidelines owing to lack of clinical data in pregnant women.

Treatment of deep vein thrombosis and pulmonary embolism in pregnancy

Low molecular weight heparin (LMWH) and unfractionated heparin (UFH) are currently recommended for the treatment of venous thromboembolism (VTE) in pregnant patients; however, LMWH is the preferred choice. The suggested treatment duration for anticoagulation in pregnant women with acute VTE is a minimum of 3 months, which includes at least 6 weeks postpartum. The optimal duration of treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) during and after pregnancy has not been studied in randomized controlled trials.

Prevention of venous thromboembolism in pregnancy

According to current guidelines, women with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) or known thrombophilia should start anticoagulant therapy as early as possible during pregnancy. Thromboprophylaxis after childbirth is not normally indicated, but may be necessary in certain cases. Appropriate risk stratification is essential to determine if thromboprophylaxis is necessary and may be used to guide the intensity of thromboprophylaxis to maintain the optimal balance between efficacy and safety. Low molecular weight heparin (LMWH) is the heparin of choice for prophylaxis in pregnant patients. Mechanical prophylactic strategies for pregnant women include: physiotherapy and exercise; use of graduated compression stockings; foot pumps; and intermittent pneumatic compression devices.

Pregnancy increases the risk of venous thromboembolism

The incidence of venous thromboembolism (VTE) in pregnant women is significantly higher than in women of a similar age who are not pregnant. Risk associated with VTE is primarily a result of hypercoagulability induced by hormonal changes. Important risk factors to consider include: increased venous stasis; pregnancy and delivery complications; a personal history of thrombosis; and inherited or acquired thrombophilia. The risk of recurrent VTE in pregnancy is also high. Diagnosis of deep vein thrombosis (DVT) in pregnant patients is usually performed by compression ultrasonography in parallel with D-dimer testing.

Investigational Strategies

There are currently no ongoing clinical trials of the newer oral direct Factor Xa and thrombin inhibitors for the prevention and/or treatment of VTE in pregnant women.