- Hereditary
- Mutations of VKORC1 Gene → Warfarin resistance
- Duplication or multiplication of Cyt P450 enzyme genes (P450 CYP2D6 & CYP2A6)
- ↑ metabolic clearance of Warfarin
- Acquired
- Poor patient compliance
- High consumption of Vitamin K
- Decreased absorption of Warfarin
- Gastroenteritis
- Coeliac disease
- Chronic pancreatitis
- Short gut syndrome
- Increased clearance of Warfarin
- Hypoalbuminemia → ↑ free fraction of Warfarin → ↑ clearance and ↓ plasma half-life
- Hyperalbuminemia → Paradoxical effect by increased binding of Warfarin
- Hyperlipidemia
- ↑ Lipids → ↑ Vitamin K pool → Warfarin resistance
- Drugs decreasing the effect of Warfarin
- Azathioprine
- Barbiturates
- Carbamazepine
- Cholestyramine
- Corticosteroids
- Dicloxacillin & Nafcillin
- Estrogen preparations
- Spironolactone → ↓ Plasma volume → ↑ Coagulation factor levels
- Griseofulvin
- Rifampicin
- Contraceptive pill
- Ritonavir
- Saint John's wort
- Sucralfate
- Tobacco smoking
- Powerful inducer of P450 (CYP1A1 & CYP1A2)
- Tobacco leaves are rich in Phylloquinone (vitamin K1)
- Each gram of Tobacco → 50 μg Vitamin K1 (exceeds the amount found in food sources)
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