Factor V Leiden
Factor V Leiden is the most common inherited thrombophilia, a point mutation that makes factor V resistant to inactivation by activated protein C and raises venous thromboembolism risk, most strongly when combined with estrogen, pregnancy, surgery, or immobility. Diagnosis is an activated protein C resistance assay followed by confirmatory factor V Leiden DNA testing, and management is standard anticoagulation for an actual thrombotic event, not for the mutation alone.
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What this article covers
- Overview
Definition: factor V Leiden is an autosomal dominant point mutation (Arg506Gln) that produces a mutant factor Va resistant to inactivation by activated protein C (APC resistance), creating a hypercoagulable state.
- Epidemiology
Population prevalence: heterozygous factor V Leiden occurs in about 5%-7% of the healthy White population; homozygous disease occurs in less than 1%.
- Risk factors
Homozygosity: the highest inherited risk, relative risk of a first VTE increased approximately 80-fold versus noncarriers.
- Pathophysiology
Normal regulation: activated factor V combines with factor X to generate thrombin; activated protein C (APC) normally cleaves and inactivates factor Va to shut this down once a clot has formed.
- Clinical features
Asymptomatic carrier state is the norm: most heterozygous carriers never develop a thrombotic event and are identified only through family or thrombophilia testing.
- Differential diagnosis
Antiphospholipid syndrome: venous or arterial thrombosis and pregnancy morbidity with persistently positive lupus anticoagulant, anticardiolipin, or anti-beta2-glycoprotein I antibodies on two…
- Diagnosis
Establish with a two-step laboratory pathway: first an activated protein C resistance (APC-R) functional assay as the screening test, and if abnormal (a shortened clotting time indicating resistance…
- Management
Isolated factor V Leiden mutation without a history of thrombosis requires no anticoagulation: an incidental or family-screening finding in a patient who has never clotted is managed with risk…
- Complications
Recurrent VTE: the main long-term risk, highest in homozygotes, compound thrombophilia, and unprovoked first events.
- Prognosis
Excellent for asymptomatic carriers: most heterozygotes never develop a thrombotic event and have normal life expectancy without treatment.
- Prevention
Avoid estrogen-containing contraceptives and menopausal hormone therapy in known carriers: offer a progestin-only or non-hormonal method; this addresses the largest modifiable risk multiplier (up to about 30-fold).
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Related articles
- Thrombophilias: an overview
Thrombophilias are inherited or acquired hypercoagulable states that predispose to venous, and in some acquired conditions arterial, thrombosis. Testing is selective and deferred until the patient is off anticoagulation and remote from acute clot, because acute thrombosis, heparin, warfarin, and estrogen all distort results, and most results do not change acute management except in antiphospholipid syndrome.
- Antiphospholipid syndrome
Antiphospholipid syndrome is an acquired autoimmune thrombophilia in which antiphospholipid antibodies cause recurrent venous and arterial thrombosis and pregnancy morbidity, paradoxically prolonging the aPTT in vitro while promoting clotting in vivo. Diagnosis requires a qualifying clinical event plus a laboratory antibody confirmed positive on two occasions at least 12 weeks apart, and thrombotic disease is treated with indefinite warfarin rather than a DOAC.
- Pulmonary embolism
Pulmonary embolism is thrombus, usually from a lower-extremity deep vein thrombosis, obstructing the pulmonary arterial circulation and causing V/Q mismatch, right ventricular strain, and hypoxemia. Diagnosis follows Wells criteria (with PERC in low-risk patients) to sequence D-dimer, CT pulmonary angiography, and V/Q scanning, and management is risk-stratified anticoagulation escalating to thrombolysis or embolectomy for hemodynamic instability.