Disease Characteristic
Factor V thrombophilia is presented by a poor anticoagulant response to activated protein C (APC) and an increased risk of venous thromboembolism.

How Common is Factor V thrombophilia?
Factor V Leiden thrombophilia is the most common inherited form of thrombophilia. Heterozygote individuals for Factor V Leiden comprise 3-8% of the general US and European populations.

Prevalence
In the US, heterozygosity for factor V Leiden is found in 5.2% of Caucasians, 2.2% of Hispanics, 1.2% of African Americans, and 1.25% of Native Americans. Individuals with current venous thromboembolism or an estrogen-related thrombosis are almost 50% heterozygote. 

Genes and Mutations (Genotype-Phenotype Relationships)
Mutation in factor V gene, which is a single amino acid replacement Arg506Glu, cause slow inactivation of factor V resulting in increased thrombin generation. The disease is inherited in an autosomal recessive manner, however heterozygote individuals also have a 5-10 fold increased risk for venous thrombosis.

Mutations and penetrance
A G-to-A mutation at nucleotide 1692 in factor V gene causes this disease. Estimated penetrance for homozygotes is 80% with a reduced penetrance of 12-20% for heterozygotes.

Phenotypes                       
Venous thromboembolism (VTE)            Pulmonary thrombosis
Deep vein thrombosis (DVT)
 
Criteria for Genetic Testing
   

    Individuals with family history of Miocardial Infarciton and VTE
    Recurrent or any type of VTE or DVT (e.g., during pregnancy)
    A first unprovoked VTE at any age
    Cancer and chemotherapy patients
   

    Venous thrombosis at unusual sites (cerebral, mesenteric, portal, hepatic)
    Women with first VTE related to Tamoxifen or selective estrogen receptor modulators (SERM)