Factor V Leiden is an inherited genetic mutation that increases the risk of forming abnormal blood clots. This mutation affects Factor V, one of the blood’s clotting proteins. While most people with the condition never develop a dangerous clot, it elevates the lifetime risk, particularly for clots in the veins of the legs or lungs. Factor V Leiden is the most common hereditary blood clotting disorder.
Understanding the Genetic Mutation
The body’s clotting system is a complex process designed to stop bleeding after an injury. A protein called Factor V acts as a cofactor to help generate thrombin, an enzyme that leads to the formation of a fibrin clot. Once bleeding is controlled, other proteins work to deactivate the clotting factors. One of these deactivating proteins, Activated Protein C (APC), specifically works to turn off Factor V to halt the clotting process.
Factor V Leiden is caused by a specific mutation in the F5 gene, which provides instructions for making the Factor V protein. This change results in an altered Factor V protein that is resistant to being inactivated by APC. Because the mutated Factor V protein remains active for longer than normal, the clotting process continues beyond what is necessary. This prolonged activity leads to a state of hypercoagulability, where the blood has an increased tendency to form clots.
The condition is inherited in an autosomal dominant pattern, meaning a person only needs to inherit one copy of the mutated gene. An individual who inherits one mutated gene from a parent is heterozygous and has a moderately increased risk of developing a blood clot. It is much rarer to inherit two copies of the mutated gene, one from each parent; this is known as being homozygous and carries a significantly higher risk of clotting.
Associated Clotting Risks and Symptoms
The Factor V Leiden mutation does not cause symptoms on its own. Symptoms only arise if a blood clot (thrombosis) forms, most commonly a deep vein thrombosis (DVT) or pulmonary embolism (PE). A DVT is a blood clot in a deep vein, most often in the legs.
The skin over the affected area may appear red or discolored. Signs of a DVT, which often occur in one leg, include:
- Swelling
- Pain
- Tenderness
- Warmth
The most immediate danger from a DVT is if a piece breaks off, becoming an embolus. If this free-floating clot travels to the lungs, it can cause a life-threatening pulmonary embolism by blocking blood flow.
Symptoms of a PE appear suddenly and require immediate medical attention. While DVT and PE are the primary concerns, the mutation is also associated with a slightly increased risk of recurrent pregnancy loss. Signs of a PE include:
- An abrupt onset of shortness of breath
- Chest pain that worsens with deep breathing
- A cough that may produce bloody sputum
- A rapid heartbeat
The Diagnosis Process
A doctor may suspect Factor V Leiden in individuals who develop a blood clot without a clear cause, especially if the event occurs before the age of 50. Other indicators that might prompt testing include having recurrent blood clots or a clot in an unusual location, such as the veins of the liver or brain. A strong family history of thrombotic events is another significant reason for a healthcare provider to investigate the possibility of an underlying genetic predisposition.
The diagnostic process involves blood tests to confirm the condition. The first is often a screening assay called the activated protein C (APC) resistance test. This test measures how the blood responds to the addition of APC; in a person with Factor V Leiden, the blood will show a reduced clotting time response, indicating resistance. About 95% of individuals with APC resistance have the Factor V Leiden mutation.
If the APC resistance test is positive, a definitive genetic test is performed to confirm the diagnosis. This test analyzes DNA from a blood sample to detect the specific mutation in the F5 gene. The genetic test also determines if a person is heterozygous (one copy) or homozygous (two copies), which helps in assessing their risk level.
Management Strategies
Management for Factor V Leiden is individualized and depends on whether a person has had a blood clot. Many people with the mutation, particularly those who are heterozygous with no history of thrombosis, may not require ongoing treatment. For these individuals, management focuses on awareness and minimizing other risk factors by maintaining a healthy weight, exercising, and avoiding smoking.
For individuals who have experienced a DVT or PE, the standard treatment involves anticoagulant medications, also known as blood thinners. These medications, such as warfarin or direct oral anticoagulants (DOACs), prevent clots from growing and reduce the formation of new ones. The duration of therapy is determined by a doctor based on the specifics of the clotting event.
Lifestyle and situational management are also important. Before any planned surgery, discuss the condition with the medical team so they can implement preventive measures. During long periods of immobility, such as extended travel, take breaks to walk and move the legs frequently to maintain blood flow. Women with Factor V Leiden should be cautious with medications containing estrogen, like oral contraceptives, as they increase clotting risk. Pregnancy also elevates this risk and requires careful monitoring.