Warfarin is an anticoagulant that works by inhibiting vitamin K epoxide reductase, which prevents vitamin K being recycled. As vitamin K is essential for the activation of factors II, VII, IX and X this decreases coagulation.

However, vitamin K is also a cofactor for protein C and protein S, both of which are inhibitors within the clotting cascade. They also have shorter half-lives than factors II, VII, IX and X. Therefore, warfarin is initially a procoagulant.

Indications for warfarin therapy include: 
  • Venous thromboembolism (DVT/PE) 
    • Target INR 2.5 (unless recurrent VTE whilst on anticoagulant, in which case target INR = 3.5) 
    • Start with heparin cover which should be continued for at least 5 days and until INR ≥ 2 for at least 24 hours, whichever is longer 
    • Duration of treatment with warfarin 
      • Proximal DVT (= popliteal vein or above) or PE: 3 months
      • Isolated calf vein DVT: 6 weeks 
    • Cancer-associated VTE: 6 months with therapeutic LMWH rather than warfarin
  • Atrial fibrillation 
    • Warfarin is not required for all AF patients 
    • If it is, target INR = 2.5 
  • Prosthetic heart valves 
    • Mechanical valves 
      • Target INR depends on valve and risk factors 
      • Risk factors: 
        • valve in mitral, tricuspid or pulmonary position
        • AF 
        • Left atrium diameter >50mm 
        • Mitral stenosis
        • LVEF <35%
      • Examples of valve types and INR
        • St Jude Medical – INR 2.5 if no risk factors, INR 3.0 if risk factors 
        • Starr-Edwards – INR 3.5 
    • Bioprosthetic valves 
      • Some require initial anticoagulation with warfarin 
  • Elective cardioversion 
    • Anticoagulate for 3 weeks prior to procedure and 4 weeks post
    • Target INR 2.5 
  • Mitral stenosis or regurgitation 
    • If warfarin indicated, target INR 2.5 

Warfarin is metabolised by cytochrome P450

Interactions with warfarin which may result in a raised INR include: 
  • Medications 
    • Antibiotics 
      • Metronidazole 
      • Erythromycin
      • Clarithromycin
      • Ciprofloxacin
      • Tetracyclines 
    • Allopurinol 
    • Amiodarone 
    • SSRIs 
    • Fluconazole
    • Cimetidine 
    • Omeprazole
  • Drinks 
    • Cranberry juice 
    • Alcohol 
  • Hyperthyroidism 

Interactions with warfarin which may result in a lower INR include
  • Rifampacin 
  • St Johns Wort 
  • Carbamazepine 
  • phenyotin 

Management of high INR
  • Major bleeding 
    • Prothrombin complex concentrate 
    • 5mg IV vitamin K 
    • FFP is suboptimal and should only be used if prothrombin complex is not available 
  • Non-major bleeding 
    • 1-3mg IV vitamin K
  • Non-bleeding INR > 8.0
    • 1-5mg oral vitamin K
  • Non-bleeding INR >5.0 
    • Withhold 1-2 doses of warfarin 
    • Reduce subsequent dose 

Warfarin is contraindicated in pregnancy as it is teratogenic

Side effects/complications of warfarin include: 
  • Haemorrhage – around 2% 
  • Alopecia 
  • Skin necrosis 
  • Purple toe syndrome 

Small print gem: warfarin possibly enhances the hypoglycaemic effect of sulphonylureas 

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