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Factor V Leiden Mutation
Principle
Certain genetic mutations increase the risk of thromboembolic complications. Some patients with recurrent venous thrombosis demonstrate activated protein C (APC) resistance despite normal protein S levels and no other detectable coagulation abnormalities. This resistance is most commonly caused by a point mutation in the Factor V (FV) gene, known as the Factor V Leiden mutation.
The mutation involves a G to A substitution at nucleotide position 1691, resulting in the replacement of arginine (Arg) at position 506 with glutamine (Gln) (FVQ506). This site is critical for APC binding, and the mutation leads to decreased inactivation of FV, promoting a hypercoagulable state.
The Factor V Leiden mutation is the most common genetic defect associated with recurrent venous thrombosis. It is also an important risk factor for obstetric complications involving maternal-fetal circulation, including severe preeclampsia, abruptio placentae, fetal growth restriction, and stillbirth.
Specimen Requirements
Specimen
Minimum Volume
Handling
Unacceptable Specimens
- Clotted samples
- Specimens not collected in EDTA tubes
- Frozen specimens
Method
Polymerase Chain Reaction (PCR) with reverse hybridization.
Normal Range
Reported as:
- Normal
- Heterozygous Mutated
- Homozygous Mutated
Turnaround Time
References
- Bertina, R. M., B. P. C. Koeleman, T. Koster, F. R. Rosendaal, R. J. Dirven, H. de Ronde, P. A. van der Velden, and P. H. Reitsma. 1994 Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64-67.
- Brenner, B., A. Zivelin, N. Lanir, J. S. Greengard, J. H. Griffin, and U. Seligsohn. 1996 Venous thromboembolism associated with double heterozygosity for R506Q mutation of factor V and for T298M mutation of protein C in a large family of a previously described homozygous protein C-deficient newborn with massive thrombosis. Blood 88:877-880.
- Kupferminic, M. J., A. Eldor, N. Steinman, A. Many, A. BarAm, A. Jaffa, G. Fait, J. B. Lessing. 1999 Increased frequency of genetic thrombophilia in women with complications of pregnancy. N. Engl. J. Med. 340:9-13.