Between 20 and 60% of patients who experience thromboembolism are found to be resistant to the effects of APC. They may have protein C present, but it cannot function in its role and inactivate factors Va and VIIIa. This is called APC resistance. Essentially all patients with hereditary APC resistance are resistant due to a single nucleotide mutation. The mutation occurs in the gene for factor V. So, APC resistance is not a defect of protein C or S, but a defect of factor V. The most common cause is a mutation in which arginine (R) at amino acid position 506 is substituted with glutamine (Q). Thus, this mutation is denoted as FV R506Q. This mutation was named 'Factor V Leiden' in 1994, after the Dutch city of Leiden, where the mutation was first identified. If patients have one or two alleles with FV R506Q, they are much more prone to thrombi.
In the United States, a single allele mutation is present in about 5% of Caucasians, 2.2% of Hispanics, and 1.2% of African American populations. The prevalence of homozygous Factor V Leiden (having two copies of the mutation) is about 1 in 5,000 persons.
