Factor V Leiden Mutation

Most common hereditary thrombophilia

Autosomal dominant inheritance pattern

Heterozygous form in 5% of white population in USA (up to 15% in Europe), 2% of Hispanic Americans, 1% in both African and Native Americans

Homozygosity in white population 1:5000

May account for 85–95% of pts with APC resistance

Relative risk of venous thrombosis sevenfold in heterozygous and 80-fold in homozygotes

VTE: DVT most likely; lower risk of PE

Risk of arterial thrombosis unknown

Hypercoagulability

DVT

Recurrent fetal loss (twofold to fivefold increased relative risk)

Conflicting data regarding association with placental abruption, severe preeclampsia, IUGR

Cerebral vein thrombosis

Renal transplant rejection

Risk of thrombosis increased by protein S deficiency, prothrombin 20210 gene mutation, hyperhomocysteinemia, OCP use, pregnancy, increasing age, immobilization, and obesity

Factor Va is a procoagulant that is inactivated by APC, with protein S as cofactor, causing less thrombin generation during the propagation phase.

FVL is resistant to inactivation by APC so thrombin generation is allowed to continue and subsequent clot formation.

FVL paradox describes the higher prevalence of FVL in pts with DVT compared with FVL pts with pulmonary embolism.

In CPB, FVL pts found to have less blood loss and need less blood transfusion during hospital stay.

Testing in FVL is the same as other causes of thrombophilia: Venous thrombosis and age <50 y; unusual sites of thrombosis (hepatic, mesenteric, cerebral); recurrent venous thrombosis; venous thrombosis with strong history of thrombotic disease, venous thrombosis in pregnant women taking oral contraceptives, relatives of pts who had venous thrombosis <50 y, MI in female smokers <50 y.

Screening test: Modified APC resistance functional assay (sensitivity and specificity for FVL close to 100%).

Confirmation test: DNA test. In liver transplant pts, DNA test positive, plasma FVL negative. In bone marrow transplant pts, DNA test negative, but plasma shows APC resistance.