Factor V Leiden is the name of the single base mutation in the gene (referred to as F5) for coagulation Factor V protein molecule. This mutation causes a missense substitution of glutamic acid for an arginine at amino acid 506 or 534 depending on the accepted start-position. Since this is the cleavage site for activated protein C (APC) to inactivate Factor V, this substitution prevents efficient inactivation of Factor V (resistance to activated protein C) resulting in an increased tendency to form abnormal blood clots that causes hypercoagulability disorder (thrombophilia). [1],[2]
Factor V Leiden which is the common inherited form of thrombophilia occurs in 3%-5% of the general population and in 20%-40% of patients with venous thromboembolic disease. The risk of blood clot mainly depends on if a person inherits one or two copies of the factor V Leiden mutation. Individuals inheriting one copy of the mutation (heterozygous for the Factor V Leiden defect ) have a 5-10 fold increased risk of thrombosis, while people inheriting two copies of the mutation (homozygous for the Factor V Leiden defect), one from each parent, may have up to 50-100 fold increased risk of developing this type of blood clot than wild-type (WT) healthy individuals. [3], [4]
The diagnosis of thrombophilia is mainly run by two methods, a screening test called a coagulation screening test or by genetic testing (DNA analysis) of the Factor V coding gene (F5 gene). Screening test is based on the relative resistance of Factor V Leiden to activated protein C (APCR) where two simultaneous tests are applied, one in the presence of activated protein C (APC) and the other in the absence and final determined ratio within two tests signify whether APC is working out or not. Activated protein C resistance assays (APCR) are quick, automated tests that can be easily performed but however may not distinguish between heterozygous and homozygous with Factor V Leiden which then may results in overlap between unaffected individuals and individuals heterozygous for Factor V Leiden. Since the treatment differ for two genotypes and DNA-based assays are not affected by other factors like pregnancy, the therapeutic use of anticoagulants, use of oral contraceptives etc., it makes the genetic testing highly reliable and desirable for using in the detection of the Factor V Leiden mutation. [5], [6]
