warfarin and aspirin

Warfarin inhibits vitamin K epoxide reductase, reducing synthesis of clotting factors II, VII, IX and X. Aspirin irreversibly inhibits platelet cyclooxygenase-1, decreasing thromboxane A2 and impairing platelet aggregation. The combined pharmacodynamic effect on haemostasis is additive, and aspirin may also displace warfarin from plasma protein binding sites, transiently increasing free warfarin concentrations.

Co-prescription significantly increases the risk of major bleeding, particularly gastrointestinal and intracranial haemorrhage. Aspirin also causes direct gastric mucosal injury, compounding the bleeding risk. The hazard is present even at low aspirin doses and persists for the lifespan of the platelet. Patients may present with melaena, epistaxis, or sudden neurological deficit.

Avoid combined use where possible, especially in patients with a high baseline bleeding risk or those requiring prolonged therapy. If the combination is necessary, use the lowest effective aspirin dose, consider gastroprotection with a proton pump inhibitor, and monitor INR more frequently. Educate the patient on signs of bleeding and advise prompt medical review if they occur.

This interaction is well established in clinical practice and supported by numerous randomised controlled trials and meta-analyses. The risk is particularly evident in patients with atrial fibrillation or mechanical heart valves.