What is the risk of venous thromboembolism (VTE) in patients taking anticoagulation therapy and hormonal contraceptives?

From the Guidelines

Patients on anticoagulation therapy who also take hormonal contraceptives face an increased risk of venous thromboembolism (VTE), and this combination should generally be avoided, especially in those with antiphospholipid antibody–positive patients, due to the potential further increase in thrombosis risk 1.

Key Considerations

• The risk of VTE in healthy women taking combined estrogen-progestin contraceptives is significantly higher than the baseline annual risk, with odds ratios ranging from 2.2 to 6.6 1.
• Progestin-only methods, such as the levonorgestrel IUD or progestin-only pill, are widely accepted as a lower-risk option for patients who require contraception but are at increased risk of thrombosis 1.
• The copper IUD is a highly effective alternative that does not increase the risk of VTE, but may increase menstrual bleeding and cramping for several months after insertion 1.

Recommendations

• Non-hormonal contraceptive methods, including copper IUDs, barrier methods, or sterilization procedures, are strongly preferred for patients on anticoagulation therapy 1.
• If hormonal contraception is necessary, progestin-only options like the levonorgestrel IUD or progestin-only pills are recommended over combined hormonal contraceptives containing estrogen 1.
• Patients should be counseled about the warning signs of VTE, including leg pain/swelling, chest pain, and shortness of breath, and should understand that anticoagulation does not completely eliminate the thrombotic risk associated with hormonal contraceptives 1.

Important Notes

• The risk of pregnancy-related VTE in the general population is higher than that seen with estrogen-progestin contraceptive use, and this should be taken into account when making contraceptive decisions for patients on anticoagulation therapy 1.
• The lack of data specific to antiphospholipid antibody–positive patients using progestin-only contraceptives must be weighed against the risk of pregnancy-related VTE in this population 1.

From the FDA Drug Label

The risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thromboembolic disease, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1. 5 to 6 for women with predisposing conditions for venous thromboembolic disease Several epidemiologic studies indicate that third generation oral contraceptives, including those containing desogestrel, are associated with a higher risk of venous thromboembolism than certain second generation oral contraceptives In general, these studies indicate an approximate two-fold increased risk, which corresponds to an additional 1 to 2 cases of venous thromboembolism per 10,000 women-years of use.

The risk of venous thromboembolism (VTE) in patients taking anticoagulation therapy and hormonal contraceptives is increased, with a relative risk of 3 to 11 for deep vein thrombosis or pulmonary embolism. Key points include:

• Increased risk: The risk of thromboembolic and thrombotic disease is well established in users of oral contraceptives.
• Relative risk: The relative risk of VTE is 3 to 11 for deep vein thrombosis or pulmonary embolism.
• Additional risk: There is an approximate two-fold increased risk of VTE with third generation oral contraceptives.
• Absolute risk: This corresponds to an additional 1 to 2 cases of VTE per 10,000 women-years of use 2.

From the Research

Risk of Venous Thromboembolism (VTE) in Patients Taking Anticoagulation Therapy and Hormonal Contraceptives

• The risk of VTE in patients taking anticoagulation therapy and hormonal contraceptives is a significant concern, as combined oral contraceptives are found in about half of VTE occurring in women aged up to 50 years 3.
• The use of progestin-only contraceptives (POCs) may also increase the risk of VTE, particularly among smokers and women with certain thrombogenic mutations, although the majority of evidence does not suggest an increase in odds for venous or arterial events with use of most POCs 4.
• Women with large uterine fibroids have a higher likelihood of VTE, and peri and postoperative management should be determined based on patient-specific risk stratification, with the majority of patients requiring short-term anticoagulation 5.
• Appropriate prophylaxis in high-risk medically ill patients has been shown to reduce the risk of VTE and related mortality, although the risk of major bleeding must be considered when choosing to implement pharmacological VTE prophylaxis 6.
• The effects of hormonal contraceptives on protein S-specific activity, a potential marker of VTE risk, have been studied, with results suggesting that dienogest may have negligible effects on protein S, while combined oral contraceptives may decrease total protein S activity and antigen levels 7.

Factors Influencing VTE Risk

• The type of hormonal contraceptive used, such as combined oral contraceptives or progestin-only contraceptives, may influence the risk of VTE 3, 4.
• Patient-specific risk factors, such as smoking, thrombogenic mutations, and large uterine fibroids, may also increase the risk of VTE 4, 5.
• The use of anticoagulation therapy may reduce the risk of VTE, although the risk of major bleeding must be considered 6.

Management of VTE Risk

• Patient-specific risk stratification is necessary to determine the appropriate management of VTE risk, including the use of anticoagulation therapy and hormonal contraceptives 5, 6.
• Consultation with a thrombosis specialist may be recommended for patients with essentially an unprovoked VTE or those with complex medical conditions 5.
• Further research is needed to confirm the utility of protein S-specific activity as a surrogate marker of VTE risk 7.