What is Factor V Leiden?

From the Guidelines

Factor V Leiden testing is recommended in women with venous thromboembolism during pregnancy or oral contraceptive use, as well as in those with a personal or family history of thromboembolism or other medical risk factors 1.

Key Considerations

• Factor V Leiden is a genetic mutation that increases the risk of blood clots by causing resistance to activated protein C, which normally helps prevent excessive blood clotting.
• People with Factor V Leiden have a 3-8 times higher risk of developing venous thromboembolism (VTE) if heterozygous (one copy of the mutation) and up to 80 times higher risk if homozygous (two copies) 1.
• Management depends on individual risk factors and history, and may include anticoagulation therapy with medications like warfarin, rivaroxaban, apixaban, or dabigatran for those who have already experienced a blood clot.
• Preventive anticoagulation may be considered during high-risk periods such as surgery, pregnancy, or prolonged immobility for those without a history of clots but with the mutation.
• Lifestyle modifications are important for all patients, including maintaining a healthy weight, staying physically active, avoiding smoking, and staying hydrated during long trips.
• Women with Factor V Leiden should discuss hormonal contraception with their doctor, as estrogen-containing contraceptives can further increase clotting risk 1.

Testing Recommendations

• Testing should be performed in at least the following circumstances: age <50, any venous thrombosis; venous thrombosis in unusual sites; recurrent venous thrombosis; venous thrombosis and a strong family history of thrombotic disease; venous thrombosis in pregnant women or women taking oral contraceptives; relatives of individuals with venous thrombosis under age 50; myocardial infarction in female smokers under age 50 1.
• Random screening of the general population for factor V Leiden is not recommended.
• Routine testing is not recommended for patients with a personal or family history of arterial thrombotic disorders, except for the special situation of myocardial infarction in young female smokers.

From the Research

Factor V Leiden and Venous Thromboembolism

• Factor V Leiden is a genetic risk factor for deep vein thrombosis, present in about 5% of the white population 2
• The risk of deep vein thrombosis among women who use oral contraceptives is greatly increased by the presence of the mutation 2, 3, 4
• The combination of factor V Leiden and oral contraceptive use may increase the risk of venous thromboembolism by 10- to 15-fold 3
• Hormone replacement therapy may also increase the risk of venous thromboembolism in women with factor V Leiden, with an estimated odds ratio of 13.16 4

Screening and Prevention

• Screening for factor V Leiden before prescribing oral contraceptives or hormone replacement therapy may be beneficial in identifying women at high risk of venous thromboembolism 2, 5
• Taking a personal and family history of deep vein thrombosis may also help identify women at risk 2
• The use of low molecular weight heparin or aspirin may help prevent pregnancy complications in women with recurrent pregnancy loss and factor V Leiden mutation 6

Risk Factors and Interactions

• Factor V Leiden interacts with other thrombophilias, such as deficiencies of antithrombin, protein C, or protein S, to increase the risk of venous thromboembolism 4
• The risk of venous thromboembolism is also increased in women with elevated levels of factor VIIIc or the prothrombin G20210A mutation 4
• The combination of factor V Leiden and hormone replacement therapy may increase the risk of venous thromboembolism, although further studies are needed to confirm this association 5, 4