Factor V Leiden results from a R506Q mutation in the F5 gene encoding factor V and is associated with increased risk of thrombophilia (OMIM# 188050). Heterozygosity for the factor V Leiden R506Q mutation is associated with resistance to activated protein C and a 5- to 10-fold increased risk of venous thrombosis. Homozygosity for this mutation is associated with resistance to APC and an approximately 80-fold increased risk of venous thrombosis. Other factors can further increase the risk of thrombosis.
Normal values: negative or no mutations are found.
Use
Factor V Leiden testing should be performed in the following cases:
A first occurrence of a venous thrombotic embolism (VTE) before age 50 years
A first unprovoked VTE at any age
A history of recurrent VTE
Venous thrombosis at unusual sites (e.g., cerebral, mesenteric, portal or hepatic veins)
VTE during pregnancy or the puerperium
VTE associated with use of oral contraceptives or hormone replacement therapy
A first VTE in an individual with a first-degree family member with VTE before age 50 years
Women with unexplained fetal loss occurring after 10 weeks of gestation
Factor V Leiden testing may be considered in the following cases:
In women with unexplained severe preeclampsia, placental abruption, or a fetus with intrauterine growth retardation
A first VTE related to the use of tamoxifen or other selective estrogen receptor modulators
Female smokers younger than age 50 years with an MI or stroke
Individuals older than age 50 years with a first provoked VTE in the absence of malignancy or an intravascular device
Asymptomatic adult family members of a known factor V Leiden proband, especially those with a strong family history of VTE at a young age
Asymptomatic female family members of probands with known factor V Leiden thrombophilia who are pregnant or who are considering oral contraceptive use or pregnancy
Women with recurrent unexplained first-trimester pregnancy loss with or without second- or third-trimester pregnancy loss
Children with arterial thrombosis
Limitations
The results of a genetic test may be affected by DNA rearrangements, blood transfusion, bone marrow transplantation, or rare sequence variations.
F5 gene mutations, other than R506Q, are not evaluated by this assay.