What is Factor V (Coagulation Factor Five) Leiden?

From the Guidelines

Factor V Leiden is a genetic mutation that significantly increases the risk of developing abnormal blood clots, particularly deep vein thrombosis (DVT) and pulmonary embolism, and management typically involves avoiding additional risk factors, considering prophylactic anticoagulation, and sometimes long-term anticoagulation with medications like warfarin, heparin, or direct oral anticoagulants for those with recurrent clots or additional risk factors.

Key Points

• Factor V Leiden is a genetic mutation that affects blood clotting by making Factor V resistant to inactivation by protein C, leading to increased clotting tendency 1.
• People with Factor V Leiden have a higher risk of developing abnormal blood clots, particularly deep vein thrombosis (DVT) in the legs or pulmonary embolism in the lungs, with those having one copy (heterozygous) having a 3-8 times higher risk of clotting, and those with two copies (homozygous) having a 50-80 times higher risk 1.
• Risk factors that further increase clotting risk include pregnancy, oral contraceptive use, hormone replacement therapy, surgery, prolonged immobility, and age 1.
• Management typically involves avoiding additional risk factors when possible, considering prophylactic anticoagulation during high-risk periods, and sometimes long-term anticoagulation with medications like warfarin, heparin, or direct oral anticoagulants for those with recurrent clots or additional risk factors 1.

Clinical Considerations

• Testing for Factor V Leiden may be useful in identifying individuals with increased recurrence risk who could then be considered for long-term antithrombotic therapy, particularly in those with a history of idiopathic venous thromboembolism or recurrent pregnancy loss 1.
• The decision to test for Factor V Leiden should take into account the coexistence of bleeding tendencies and other contraindications, as well as the potential benefits and harms of long-term anticoagulation therapy 1.
• Asymptomatic family members of individuals with Factor V Leiden may also benefit from testing to determine their risk of venous thrombosis and guide antithrombotic prophylaxis during high-risk periods 1.

From the Research

Factor Five and Lyden

• Factor V Leiden (FVL) is a genetic mutation that increases the risk of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE) 2, 3, 4.
• Studies have shown that FVL carriers have a higher risk of isolated symptomatic DVT compared to symptomatic PE with or without DVT 2, 3.
• The prevalence of asymptomatic PE does not differ between FVL positive and negative groups, while the rate of asymptomatic DVT tends to be higher in FVL negative groups 2.
• FVL is also associated with an increased risk of VTE in cancer patients, with a hazard ratio of 2.0 (95% confidence interval 1.0-4.0) 5.
• The risk of recurrent VTE is increased by 46% in patients with heterozygous FVL mutation, according to a systematic review and meta-analysis 6.

Clinical Implications

• The FVL paradox, which refers to the different risk of DVT and PE in FVL carriers, has been confirmed in several studies 2, 3.
• FVL carriers have a higher risk of proximal DVT location compared to non-carriers 2.
• Increasing age and unprovoked nature of VTE event carry a higher risk of symptomatic PE 2.
• FVL can be used for individual risk assignment in cancer patients 5.

Risk Factors

• FVL is a genetically determined risk factor for VTE, and its presence can increase the risk of recurrent VTE 6.
• Other thrombophilic defects, such as factor II 20210A, do not show a similar paradox in carriers 3.
• The risk of pulmonary embolization may vary among patients with different causes of venous thromboses 4.