Factor V Leiden (Activated Protein C Resistance)

The Factor V Leiden mutation (FVL) was identified in 1993 and has since been found to be a leading cause of Venous Thromboembolism among white populations. FVL, a single nucleotide point mutationnin the coagulation factor V (FV) gene, represents the most common genetic risk factor for VTE. This mutation produces an altered FV commonly known as “Leiden” protein, which is responsible for the development of thrombosis. The FVL mutation makes the FV coagulation resistant to down-regulation by activated protein C.

Population Frequency of Factor V Leiden (FVL)

The population frequency of FVL mutation is high. Heterozygous FVL mutation is found in 5% to 10% of caucasian individuals and in up to 30% of patients with VTE. Thus FVL mutation is by far the most common inherited risk factor for VTE. Although conventionally FVL is referred to as a “mutation,” it is actually the most common single nucleotide polymorphism within the FV gene. It is very uncommon in African Americans, Hispanics and Asians.

Risk of VTE Associated with FVL Mutation

  • Risk of VTE in FVL homozygotes: FVL homozygotes have only the Leiden protein and an 80-fold increased risk of VTE compared to the general unaffected population.
  • Risk of VTE in FVL heterozygotes: FVL heterozygotes are believed to produce about 50% of Leiden protein and have a 5- to 7-fold increased risk of VTE compared to the general population. It is important to underscore that Factor V Leiden by itself does not cause thrombosis in individuals who are heterozygous for this mutation; usually a precipitating event is required.

Most blood clots in a heterozygous individual occur in association with some external cause or “trigger.” Common triggers are pregnancy, the use of birth control pills, hormone replacement therapy after menopause, and blood clots. Especially blood clots that may occur after surgery or an injury, specifically injuries to the leg. Not everyone with heterozygous factor V Leiden develops a blood clot. For some people with heterozygous factor V Leiden, there is no history of abnormal blood clotting in their parents.