Factor V Leiden: A genetic disorder of blood coagulation (clotting) that carries an increased risk of venous thromboembolism -- the formation of clots in veins that may break loose and travel through the bloodstream to the lungs or brain. On the molecular level, factor V Leiden is characterized by a G to A substitution at nucleotide 1691 in the gene for factor V that causes a single amino acid replacement in the factor V protein. On the clotting level, factor V Leiden is inactivated about 10 times slower than normal factor V and persists longer in the circulation, resulting in increased generation of thrombin and a hypercoagulable state (thrombophilia).
Factor V Leiden is the most common inherited disorder of blood clotting in the US, affecting 5% of Caucasians and 1.2% of African Americans. Individuals heterozygous for the factor V Leiden mutation (with one copy of it) have a slightly increased risk for venous thrombosis. Homozygous individuals (with two copies of the mutation) have a much greater risk of venous thrombosis. The diagnosis of factor V Leiden thrombophilia is made by a coagulation test or DNA analysis of the factor V gene. Therapy for Factor V Leiden is usually initiated only after a clot - often one that is unexpected and spontaneous-has occurred and an evaluation has discovered the presence of the mutation. Therapy may involve heparin, warfarin and low-molecular-weight heparins. Newer anticoagulants such as direct thrombin inhibitors may have a role to play here in the future.