What is Factor V Leiden (Factor 5 Leiden) thrombophilia?

From the Guidelines

Factor V Leiden (Factor 5 Leiden) Thrombophilia is a genetic disorder characterized by a mutation in the factor 5 gene, leading to an increased risk of thrombosis 1. This mutation results in activated protein C resistance, which is the most common recognized abnormality of coagulation among patients with venous thromboembolism 1. Individuals with Factor V Leiden may require anticoagulation therapy, such as warfarin or rivaroxaban, to prevent recurrent venous thromboembolism 1.

Key Points

• Factor V Leiden is a genetic disorder that increases the risk of thrombosis, particularly venous thromboembolism 1.
• The mutation leads to activated protein C resistance, which is the most common recognized abnormality of coagulation among patients with venous thromboembolism 1.
• Individuals with Factor V Leiden may require anticoagulation therapy, such as warfarin or rivaroxaban, to prevent recurrent venous thromboembolism 1.
• The duration of anticoagulation therapy is typically lifelong, with regular monitoring of international normalized ratio (INR) levels for warfarin therapy, aiming for a target INR range of 2.0-3.0 1.

Management

• Testing for Factor V Leiden may be useful in identifying individuals with increased recurrence risk who could benefit from long-term antithrombotic therapy 1.
• Anticoagulation therapy, such as warfarin or rivaroxaban, may be recommended for individuals with Factor V Leiden who have experienced a venous thromboembolic event 1.
• The decision to initiate anticoagulation therapy should take into account the individual's risk of recurrent thrombosis, as well as their risk of anticoagulant-related bleeding 1.

Special Considerations

• Factor V Leiden has also been associated with increased risk of recurrent pregnancy loss, placental infarction, and other pregnancy-related complications 1.
• Women with Factor V Leiden may require special consideration during pregnancy, including antithrombotic prophylaxis and close monitoring for signs of thrombosis 1.

From the Research

Definition and Overview of Factor V Leiden Thrombophilia

• Factor V Leiden thrombophilia is a genetic disorder characterized by a poor anticoagulant response to activated protein C and an increased risk for venous thromboembolism 2.
• It is caused by a mutation in the gene coding for coagulation factor V, resulting in resistance to activated protein C 3, 4, 5.

Clinical Manifestations and Risks

• Deep venous thrombosis and pulmonary embolism are the most common manifestations of Factor V Leiden thrombophilia 2.
• The risk of recurrent venous thromboembolism is significantly higher in carriers of the Factor V Leiden mutation than in patients without this abnormality 3, 5.
• The mutation is also associated with a 2- to 3-fold increased relative risk for pregnancy loss and possibly other obstetric complications 2.

Diagnosis and Treatment

• Diagnosis of Factor V Leiden thrombophilia requires the activated protein C resistance assay or DNA analysis of the F5 gene 2.
• The first acute thrombosis is treated according to standard guidelines, and decisions regarding the optimal duration of anticoagulation are based on an individualized assessment of the risks for venous thromboembolism recurrence and anticoagulant-related bleeding 2.
• In the absence of a history of thrombosis, long-term anticoagulation is not routinely recommended for asymptomatic Factor V Leiden heterozygotes, although prophylactic anticoagulation may be considered in high-risk clinical settings 2.

Genetic Modulation and Risk Factors

• The risk of venous thromboembolism in Factor V Leiden heterozygotes is modulated by common F5 single-nucleotide polymorphisms (SNPs) that affect the FV(Leiden)/normal FV ratio in plasma 4.
• The presence of other genetic or acquired thrombophilic disorders, as well as circumstantial risk factors, can influence the clinical expression of Factor V Leiden thrombophilia 2.
• Homozygous and compound heterozygous Factor V Leiden and prothrombin G20210A mutations confer a high risk of thrombosis recurrence, with a rate of recurrent thromboembolism of 59% 6.