What is Factor V (Coagulation Factor Five) Leiden?

From the Guidelines

Factor V Leiden is a significant risk factor for venous thromboembolism, and testing for this mutation can be crucial in identifying individuals at high risk of recurrence, particularly those with a history of idiopathic venous thromboembolism or with additional clotting disorders 1.

Key Points

• Factor V Leiden is a genetic mutation that affects the Factor V protein, leading to an increased risk of developing abnormal blood clots.
• The mutation is relatively common, affecting about 3-8% of people with European ancestry, and is inherited in an autosomal dominant pattern.
• People with this mutation may have a 3-8 times higher risk of developing deep vein thrombosis or pulmonary embolism compared to those without it.
• Certain situations increase the risk of clot formation, including pregnancy, oral contraceptive use, hormone replacement therapy, surgery, prolonged immobility, or having additional clotting disorders.
• Management typically involves avoiding risk factors when possible, and in some cases, preventive blood thinners during high-risk periods.
• Those with a history of blood clots may require long-term anticoagulation therapy with medications like warfarin, heparin, or direct oral anticoagulants.

Testing and Identification

• Testing for Factor V Leiden can be useful in identifying individuals at high risk of recurrence, particularly those with a history of idiopathic venous thromboembolism or with additional clotting disorders 1.
• The American College of Medical Genetics recommends testing for Factor V Leiden in patients with a history of venous thromboembolism, particularly those with a family history of the condition 1.
• The EGAPP Working Group recommends routine testing for Factor V Leiden and prothrombin mutations in adults with a history of idiopathic venous thromboembolism and their adult family members 1.

Risk Assessment and Management

• The risk of recurrence is highest during the first 6-12 months after the event, with a cumulative recurrence rate of about 30% by 8-10 years 1.
• Patients with persistent risk factors for venous thromboembolism, such as cancer, stroke with extremity paresis, or obesity, are at highest risk for recurrence.
• Lifetime antithrombotic prophylaxis should be considered for homozygotes after a thrombotic event, as well as for those with a history of recurrent venous thromboembolism 1.
• The decision to use anticoagulation therapy should take into account the coexistence of bleeding tendencies and other contraindications.

From the Research

Factor Five and Lyden

• Factor V Leiden (FVL) is a genetic disorder that increases the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) 2, 3, 4
• Studies have shown that FVL carriers have a higher prevalence of isolated symptomatic DVT compared to symptomatic PE with/without DVT 2, 3
• The FVL paradox refers to the different risk of DVT and PE in carriers of FVL, with a higher risk of DVT and a lower risk of PE 2, 3
• The risk of recurrent venous thromboembolism (VTE) is increased by 46% in patients with heterozygous FVL mutation 5
• FVL mutation is also a risk factor for VTE in cancer patients, with a hazard ratio of 2.0 (95% confidence interval 1.0-4.0) 6

Clinical Implications

• The FVL paradox may have clinical implications, such as a relatively lower risk of PE in FVL positive patients 2
• FVL carriers may require closer monitoring and treatment to prevent DVT and PE 3, 5, 6
• The presence of FVL mutation may be used for individual risk assignment in cancer patients 6

Prevalence of FVL

• The prevalence of FVL varies among different populations, with a higher prevalence in patients with DVT and a lower prevalence in patients with isolated PE 2, 3, 4
• FVL is more common among patients with deep vein thrombosis (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.2 to 3.7; P = 0.006) or both pulmonary embolism and deep vein thrombosis (OR = 1.8; 95% CI: 1.0 to 3.3; P = 0.07) than among patients with isolated pulmonary embolism 4