Factor V Leiden
- Factor V Leiden (FVL) is a genetic point mutation in the F5 gene at the activated protein C (APC) cleavage site on the factor V and Va molecule leading to increase in thrombin and as a result leads to clot formation. This is the most common form of inherited thrombophilia.
- System(s) affected: cardiovascular, gastrointestinal, hemo/lymphatic/immunologic, nervous, pulmonary, reproductive
- Synonym(s): FVL thrombophilia; FVL mutation, hereditary APC resistance
- The incidence of venous thrombosis in healthy children is extremely low (0.07/100,000 per year).
- There is a weak, however significant, association between procoagulant states (including FVL) and coronary events in younger patients.
- 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).
- ~5–8% occurrence of heterozygosity in Caucasians, Hispanic Americans ~2%, African Americans ~1%, and Asian Americans ~0.45% of those heterozygous for FVL small percentage of individuals develop VTE, estimated 5–10%
- General population 4–5% without history of venous thromboembolism (VTE); 12–14% reported in parts of Greece, Sweden, and Lebanon. No reports seen in Chinese or Japanese.
Etiology and Pathophysiology
- Factor V is a protein that is part of the clotting cascade that 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 factors V, Va, and VIII, thereby keeping the clotting cascade in check (negative feedback loop).
- In FVL, a point mutation at the binding site of APC (Arg506Glu) renders it less able to cleave factor V or Va. This 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 for VTE is ~7-fold in heterozygous and ~80-fold in homozygous factor V Leiden individuals, compared with individuals without the mutation. 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 FVL, that risk is compounded.
- In men with an underlying thrombophilia, testosterone therapy can promote VTE.
- Pregnancy and homozygous FVL 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.
- 30% of patients with VTE is attributed to FVL and prothrombin mutation G20210A; however, the risk is weaker compared to antithrombin III, protein C and protein S deficiency, which is around 1% in the general population.
- FVL versus general population, a modest increase in the recurrence risk of VTE is seen.
Patients with FVL without thrombosis do not require prophylactic anticoagulation.
Commonly Associated Conditions
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