- Etiology/Pathophysiology
- Most common inherited hypercoagulable disorder (3-5% of Caucasians)
- Point mutation in Factor V gene (G1691A) → Factor V becomes resistant to inactivation by Protein C
- Results in activated Protein C (APC) resistance
- Autosomal dominant inheritance; homozygotes have higher thrombotic risk than heterozygotes
- Clinical Features
- Increased risk of venous thromboembolism (VTE): DVT, PE
- Heterozygotes: 5-10x ↑ risk of VTE
- Homozygotes: 50-100x ↑ risk of VTE
- Risk further ↑ with: OCPs, pregnancy, surgery, prolonged immobilization
- Recurrent pregnancy loss (due to placental thrombosis)
- Arterial thrombosis is rare (unlike antiphospholipid syndrome)
- Diagnostics
- APC resistance assay: Functional test showing resistance to activated Protein C
- Genetic testing: Confirms Factor V Leiden mutation (definitive)
- Consider testing in: Young pts with VTE (<50 yrs), recurrent VTE, family Hx of VTE, VTE in unusual sites
- Treatment
- Asymptomatic carriers: No prophylactic anticoagulation; avoid OCPs, counsel about risk factors
- Acute VTE: Standard anticoagulation (heparin → warfarin or DOACs)
- Recurrent VTE: Consider long-term anticoagulation
- Pregnancy: Prophylactic LMWH if prior VTE or high-risk features
- Avoid estrogen-containing contraceptives (use progestin-only or non-hormonal methods)
- Key Associations
- Think Factor V Leiden in young Caucasian pt with unprovoked VTE
- Most common cause of APC resistance
- Does NOT cause arterial clots (unlike antiphospholipid syndrome)