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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