Thrombophilia: How To Test? How To Manage?

By Julie Hambleton, MD

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Factor V Leiden

The factor V Leiden mutation is a single-point mutation in the gene encoding coagulation factor V, resulting in the replacement of arginine by glutamine at a key proteolytic site on the activated factor V protein. The mutated molecule cannot be cleaved by activated protein C—hence the so-called APC resistance. Factor V clotting activity is normal in in vitro coagulation assays. Rather, factor V is resistant to inactivation in vivo. The factor V Leiden mutation is found in 2 to 5% of the asymptomatic Caucasian population, making it a far more common abnormality overall than the AT, PC, and PS deficiencies combined. The factor V Leiden mutation is very uncommon in the African-American and Asian populations. For asymptomatic individuals, the relative risk for developing unprovoked VTE is increased about sevenfold for heterozygotes and 80-fold for homozygotes. Nonetheless, < 50% of heterozygous individuals will develop VTE in their lifetime. In unselected patients who do present with a first unprovoked DVT, approximately 40% will be identified as heterozygotes for the factor V Leiden mutation. The presence of the factor V Leiden mutation has also been associated with an increased risk for venous thrombosis during use of oral contraceptives, during pregnancy, and when combined with other genetic and acquired abnormalities of anticoagulation, such as PC and PS deficiencies.

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