Warfarin is an oral anticoagulant that was used first-line for many years in both the management of venous thromboembolism and reducing stroke risk in patients with atrial fibrillation. It has now been largely superseded by the use of direct oral anticoagulants (DOACs) which do not require the same level of monitoring as warfarin.

Mechanism of action

• inhibits epoxide reductase preventing the reduction of vitamin K to its active hydroquinone form
• this in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C.
  • Warfarin affects factor IX less prominantly than factor VII, therefore the APTT is usually normal in patients taking Warfarin with a prolonged PT

Indications

• mechanical heart valves
  • target INR depends on the valve type and location
  • mitral valves generally require a higher INR than aortic valves.
• second-line after DOACs:
  • venous thromboembolism: target INR = 2.5, if recurrent 3.5
  • atrial fibrillation, target INR = 2.5

Monitoring

• patients are monitored using the INR (international normalised ratio), the ratio of the prothrombin time for the patient over the normal prothrombin time.
• warfarin has a long half-life and achieving a stable INR may take several days
  • Start with a LMWH for bridging until INR is 2
• there are a variety of loading regimes and computer software is now often used to alter the dose

Factors that may potentiate warfarin

• liver disease
• P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin
• cranberry juice
• drugs which displace warfarin from plasma albumin, e.g. NSAIDs