Factor V Leiden
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- Factor V Leiden is a genetic mutation at the activated protein C (APC) cleavage site on the factor V and Va molecule leading to the most common form of inherited thrombophilia.
- System(s) affected: cardiovascular, gastrointestinal, hemo-/lymphatic/immunologic, nervous, pulmonary, reproductive
- Synonym(s): factor V Leiden thrombophilia; factor V Leiden mutation, hereditary APC resistance
Potential for increased thrombosis risk in patients with factor V Leiden and concomitant risks
- Recurrent pregnancy loss is a possible complication.
- Increased thrombotic risk in pregnancy and postpartum (additive) especially in homozygous state
- Possible increased risk of IUGR, preeclampsia, placental abruption, evidence mixed
Studies estimate ~5–8% occurrence of heterozygosity in Caucasians, Hispanic Americans ~2 %, African American ~1%, and Asian Americans ~0.45%.
Etiology and Pathophysiology
- Factor V circulates in the plasma. When exposed to tissue factor, factor V amplifies the production of thrombin which further promotes clotting by activating factor V into procoagulant factor Va.
- For balance, thrombin also promotes APC production which will cleave and inactivate factor V, Va, and VIII, thereby keeping the clotting cascade in check (negative feedback loop).
- In factor V Leiden, a point mutation at the binding site of APC (Arg506Glu) renders it less able to cleave factor V or Va. This, in turn, reduces the anticoagulant role of factor V as a cofactor to APC and increases the procoagulant role of activated factor V, as there is now 20-fold slower degradation of factor Va.
- Risk for venous thromboembolism (VTE) is ~7-fold in heterozygous and ~80-fold in homozygous factor V Leiden individuals, compared with individuals without the mutation (1). This risk is compounded/increased by the presence of the following:
- Having non-O blood type (A, B, or AB) (2- to 4-fold)
- Oral contraceptives: homozygotes up to 100-fold; heterozygotes, 35-fold. The increased risk is halved when the patient uses desogestrel-containing oral contraceptives.
- Hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs) both increase the risk of thrombosis; in patients with factor V Leiden, that risk is compounded.
- Pregnancy and homozygous factor V Leiden increase the risk of thrombosis 7- to 16-fold during pregnancy and the puerperium.
- Data are conflicting with regard to risk for recurrent VTE for patients with factor V Leiden but trend toward an increased risk (2,3).
Patients with factor V Leiden without thrombosis do not require prophylactic anticoagulation.
Commonly Associated Conditions