The Factor V Leiden mutation is due to a single base-pair change (point mutation) in the gene for Factor V (sometimes referred to as the F5 gene). Technically, this amounts to a substitution of the nucleic acid adenine (A) for a normal guanine (G) at position 1691, which leads to an amino acid substitution of arginine (R) for a normal glutamine (Q) at position 506 within the protein. The normal function of Factor V is to serve as a cofactor in blood coagulation in conjunction with Factor X. Activated protein C (aPC) normally degrades Factor V to limit clotting. The mutation alters Factor V's protein's structure so that aPC can not degrade Factor V normally so that abnormal clotting is enhanced. Individuals may carry the mutation on one chromosome (heterozygous) or on both chromosomes (homozygous). Heterozygotes have a 7-fold increased risk of developing thrombosis, while individuals who are homozygous for the mutation have up to an 80-fold increased risk. For heterozygous patients using oral contraceptives, the risk of thrombosis increases to 30-fold.

The Factor V Leiden polymorphism should be evaluated in patients for whom testing is undertaken to identify risk factors associated with venothrombotic disease, including activated protein C resistance, and deficiencies of protein S, protein C, and antithrombin. The Factor V Leiden mutation is assessed in the laboratory using technologies that enable identification of the single base pair change. Results are reported as homozygous wild-type (no mutation detected), heterozygous (mutation detected on a single chromosome), and homozygous mutant (mutation detected on both chromosomes). Because this is a genetic test, this test only needs to be performed once in a patient’s lifetime.