Overview
Definition
An inherited hypercoagulable state caused by a genetic mutation in clotting Factor V, making it resistant to inactivation by Activated Protein C.
Epidemiology
The most common inherited thrombophilia in Caucasians (prevalence ~5% of population).
Etiology & Risk Factors
- Point mutation in the F5 gene (G1691A substitution, replacing arginine with glutamine at position 506), preventing cleavage by Activated Protein C
Clinical Symptoms
- Increased risk of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)
- Often asymptomatic until exposed to additional risk factors (surgery, pregnancy, oral contraceptives)
- *Note: Does NOT increase risk of arterial thrombosis (Stroke, MI)*
Clinical Approach
Diagnosis
- Activated Protein C (APC) resistance test
- Genetic testing showing heterozygous or homozygous Factor V Leiden mutation
Management
- Prophylactic anticoagulation is NOT routinely indicated for asymptomatic carriers
- Anticoagulation (DOACs or Warfarin) for standard duration if a provoked or unprovoked VTE occurs
- Prophylaxis during high-risk periods (surgeries)
Complications
- Recurrent venous thromboembolism
- Pulmonary embolism (potentially fatal)
- Pregnancy complications (fetal loss)