Factor V Leiden ∞ Area

Factor V Leiden

Meaning

Factor V Leiden is a specific genetic mutation within the F5 gene, leading to a modified Factor V protein that exhibits resistance to inactivation by activated protein C. This alteration results in a sustained procoagulant state, meaning the blood has an increased tendency to form clots, contributing to a condition known as thrombophilia.

Context

This genetic variant operates within the complex physiological system of hemostasis, specifically impacting the coagulation cascade responsible for blood clot formation. Factor V normally functions as a critical cofactor in the generation of thrombin, a key enzyme in clotting. The Leiden mutation disrupts the natural regulatory mechanism that balances clot formation and dissolution, shifting the system towards excessive clot propagation.

Significance

Understanding Factor V Leiden is clinically important because it represents the most common inherited cause of venous thromboembolism, including deep vein thrombosis and pulmonary embolism. Identifying this genetic predisposition allows healthcare professionals to assess an individual’s risk for thrombotic events, particularly in situations such as pregnancy, surgery, or when considering hormonal therapies, thereby guiding appropriate preventative strategies.

Mechanism

The underlying mechanism involves a single nucleotide substitution, G to A at position 1691 in the F5 gene, which translates to an amino acid change from arginine to glutamine at position 506 in the Factor V protein. This specific alteration eliminates a cleavage site for activated protein C, a natural anticoagulant. Consequently, Factor Va, the activated form, remains active for a longer duration, leading to increased thrombin production and an elevated risk of clot formation.

Application

Genetic testing for Factor V Leiden is frequently considered for individuals who experience unexplained thrombotic episodes, have a family history of venous thromboembolism, or prior to initiating certain medications known to increase clotting risk. Clinical management for carriers often involves patient education about risk factors and, for some, may include prophylactic anticoagulant therapy during periods of high thrombotic risk, such as extended immobility or major surgical procedures.

Metric

The presence of Factor V Leiden is primarily confirmed through molecular genetic testing, which directly detects the specific G1691A mutation in the F5 gene from a blood sample. Functional assays, such as the activated protein C resistance assay, can also indicate a functional resistance to APC, suggesting the potential presence of the mutation, though genetic confirmation remains the definitive diagnostic method.

Risk

Individuals carrying the Factor V Leiden mutation face an elevated lifetime risk of developing venous thromboembolism, which can lead to serious health complications like deep vein thrombosis or pulmonary embolism. This risk is further amplified by additional factors such as obesity, prolonged immobility, certain surgical procedures, pregnancy, or the use of estrogen-containing contraceptives or hormone replacement therapy, necessitating careful clinical oversight and risk mitigation.

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HRTioJuly 19, 2025