Factor V Leiden (FVL) is the most frequently inherited blood clotting disorder, characterized by a genetic change that affects the body’s natural ability to regulate coagulation. This condition is a form of thrombophilia, meaning it increases the tendency to form abnormal blood clots. While many people with FVL may never experience a clotting event, its presence elevates the risk, particularly when combined with other factors. Understanding the underlying genetic mechanism and associated health risks is key to management.
The Genetics of Factor V Leiden
Factor V Leiden stems from a specific alteration within the F5 gene, which provides instructions for making the coagulation protein Factor V. Normally, Factor V accelerates the production of fibrin, the material that forms the meshwork of a blood clot. Once a clot forms, the natural anticoagulant Activated Protein C (APC) deactivates Factor V to stop the clotting process.
The FVL mutation involves a single DNA change, known as the R506Q substitution. This change replaces the amino acid arginine with glutamine at position 506 of the Factor V protein. This substitution occurs precisely where APC is supposed to bind and cleave Factor V to inactivate it. Consequently, the mutated Factor V Leiden protein is partially resistant to inactivation by APC.
This resistance means the Factor V Leiden protein remains active longer than normal, resulting in hypercoagulability. The delay in turning off the clotting cascade leads to an increased and prolonged production of thrombin, which promotes excessive clot formation. This defect in the body’s natural “off switch” is the biological basis for the increased risk associated with FVL.
Primary Health Risks Associated with FVL
The primary clinical consequence of Factor V Leiden is an increased susceptibility to Venous Thromboembolism (VTE). VTE encompasses two major conditions: Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). A DVT is the formation of a blood clot, most commonly in the deep veins of the legs. A PE occurs if a portion of that clot breaks free and travels through the bloodstream to lodge in the arteries of the lungs, a potentially life-threatening event.
The level of VTE risk is directly related to the inheritance pattern of the mutation. Most individuals inherit one copy of the mutated gene, a state known as heterozygosity. Heterozygous carriers have an approximate five- to seven-fold increased lifetime risk of developing a first DVT compared to the general population, but the absolute risk remains relatively low.
A much smaller number inherit two copies of the mutated gene, one from each parent, which is known as homozygosity. This condition significantly amplifies the risk, increasing the chance of a VTE by approximately 20- to 50-fold. In both cases, the presence of FVL does not guarantee a clot but makes the body more vulnerable when other risk factors are present.
The risk is compounded by circumstantial factors, which can trigger a clotting event. Women using estrogen-containing oral contraceptives or hormone replacement therapy face a significantly elevated risk, which can be up to 35-fold higher. Other temporary risk factors include prolonged immobility, such as during long-haul travel or following major surgery, as well as pregnancy and the postpartum period.
Testing and Confirmation of FVL Status
Testing for Factor V Leiden is generally recommended for individuals who have experienced an unexplained blood clot, particularly at a young age (under 50), or who have a strong family history of VTE. Testing may also be considered for those who have experienced clots in unusual locations, such as the cerebral or portal veins.
The diagnostic process typically begins with a functional screening test called the Activated Protein C Resistance assay (APC-R assay). This blood test measures how well a patient’s plasma responds to APC. If the plasma clots faster than expected in the presence of APC, it suggests resistance, which is present in over 90% of FVL cases.
If the screening test indicates resistance, a confirmatory genetic test is then performed. This test, usually DNA analysis of the F5 gene, directly looks for the R506Q mutation. The genetic test is highly specific and is necessary to confirm the FVL diagnosis and determine whether the individual is a heterozygous carrier (one copy) or a homozygous carrier (two copies). This confirmation of FVL status is essential for accurate risk assessment and informing long-term health management.
Managing Life with Factor V Leiden
For the majority of individuals who test positive for Factor V Leiden but have never experienced a blood clot, continuous anticoagulant medication is typically not recommended. The focus for these asymptomatic carriers is proactive risk reduction and education. Understanding the symptoms of DVT and PE is important so that medical attention can be sought immediately if an event occurs.
If a person with FVL experiences a VTE, the standard treatment involves a course of anticoagulant therapy, commonly referred to as blood thinners. Treatment often starts with injectables like heparin, followed by a transition to oral anticoagulants such as warfarin or direct oral anticoagulants (DOACs). The duration of this treatment is individualized, often lasting three to six months for a first clot. However, treatment may be extended indefinitely for recurrent events or in cases with other compounding risk factors.
Lifestyle Management
Lifestyle adjustments are a continuous part of managing FVL status.
- Maintaining a healthy body weight and engaging in regular physical activity promote healthy blood flow and reduce overall VTE risk.
- Avoid prolonged periods of immobility, especially during travel or recovery from illness. This often means standing up and moving the legs every hour.
- Individuals with FVL should discuss alternative contraception or hormone replacement options with their healthcare provider, as estrogen-containing therapies are generally discouraged due to their synergistic effect on clotting risk.