Description

• 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

Pediatric Considerations
Potential for increased thrombosis risk in patients with factor V Leiden and concomitant risks

Pregnancy Considerations

• 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
• Women with a history of adverse pregnancy outcomes should be tested for thrombophilia if they are planning a future pregnancy (1).

Epidemiology

Prevalence
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 because there is now 20-fold slower degradation of factor Va.

Risk Factors

• 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 (2). 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.
  • In men with an underlying thrombophilia, testosterone therapy can promote VTE (3).
  • Pregnancy and homozygous factor V Leiden increase the risk of thrombosis 7- to 16-fold during pregnancy and the puerperium.
  • Those with combined thrombophilias and end-stage renal disease are at risk for developing calciphylaxis (4).
• Data are conflicting with regard to risk for recurrent VTE for patients with factor V Leiden but trend toward an increased risk (5,6).

General Prevention

ALERT
Patients with factor V Leiden without thrombosis do not require prophylactic anticoagulation.

Commonly Associated Conditions

Venous thrombosis