Factor V Leiden With Reflex to R2

The factor V Leiden mutation causes activated protein C (APC) resistance and increases the risk for venous thrombosis and pulmonary embolism. Heterozygotes (with one copy of the mutation) have a sevenfold increased risk, and homozygotes (with two copies) have a 50% to 80% increased risk. These risks are elevated further by additional genetic defects in naturally occurring anticoagulant proteins (eg, deficiencies of protein C, protein S, or antithrombin) and by situations that tend to provoke thrombosis (eg, major surgery, oral contraceptive use, pregnancy, malignancy, immobility). Factor V Leiden is also associated with increased risk for multiple pregnancy loss. Factor V Leiden is present in 5% to 7% of the general population and 20% to 40% of individuals with venous thrombosis.

The factor V R2 polymorphism is associated with decreased levels of factor V and it significantly increases risk of venous thrombosis in individuals who are heterozygous for the factor V Leiden mutation. Coexistence of the R2 polymorphism with factor V Leiden increases the risk for venous thrombosis approximately to a 16-fold increased risk. The average age of the first thrombotic event is six years younger in individuals who are heterozygous for both factor V Leiden and the R2 polymorphism than in those with factor V Leiden alone. The R2 polymorphism is common in the general population, with one copy (heterozygous) in 10% of individuals. Among patients with venous thrombosis, approximately 12% are heterozygous for the R2 polymorphism. Indications for testing: Venous thrombosis, pulmonary embolism, peripheral vascular disease (particularly lower extremity occlusive disease), premature stroke or transient ischemic attack, myocardial infarction in female smokers under age 50, women with multiple pregnancy loss. Also, family history of venous thrombosis or a relative known to have the factor V Leiden mutation. Factor V R2 DNA analysis will automatically be performed on the same sample for individuals found to be heterozygous for the factor V Leiden mutation.