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 the Afro-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. Effective therapy is available and may involve heparin, warfarin and low-molecular-weight heparins.

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