Description

• Most commonly prescribed oral anticoagulant
• Inhibits vitamin K metabolism required for activation of factors II, VII, IX, and X
• Blocks the coagulation cascade's extrinsic system and common pathway
• Commonly used for venous thromboembolism and prevention of embolism with prosthetic heart valves or atrial fibrillation
• Adjustments based on the international normalization ratio (INR):
  • Typical therapeutic range 2–3
  • 2.5–3.5 for mechanical valves and antiphospholipid syndromes
• Contraindications include any condition in which the risk of hemorrhage or adverse reaction outweighs clinical benefit:
  • Prior hypersensitivity
  • Skin reactions
  • Recent surgeries
  • Active or potential GI, intracerebral, or genitourinary bleeding
  • Fall risk

Etiology

• Bleeding complications:
  • 15% of patients/yr:
    • 4.9% major bleeding events
    • Up to 0.8% fatal, most commonly intracranial hemorrhage (ICH)
  • Bleeding risk is directly related to INR:
    • Increases dramatically above 4
• Risk factors for nontherapeutic INR:
  • Age >75 yr
  • Hypertension, cerebrovascular disease, severe heart disease
  • Diabetes, renal insufficiency
  • Alcoholism or liver disease
  • Hypermetabolic states, fever
  • Hyperthyroidism
  • Cancer
  • Collagen vascular disease
  • Hereditary warfarin resistance
  • Cytochrome P450 polymorphism

• Pregnancy class X
• Crosses the placenta causing spontaneous abortion and birth defects