Major
Established
Description
Concurrent use significantly increases bleeding risk through dual anticoagulant/antiplatelet mechanisms. Even low-dose aspirin (81 mg) meaningfully raises the risk of major hemorrhage.
Mechanism
Aspirin irreversibly inhibits COX-1-mediated thromboxane A2 synthesis, impairing platelet aggregation; additionally, aspirin may displace warfarin from plasma proteins and inhibit hepatic CYP2C9, increasing warfarin exposure.
Clinical Significance
Meta-analyses demonstrate a 2- to 3-fold increase in major bleeding events when aspirin is added to warfarin therapy.
Management
Avoid combination unless clearly indicated (e.g., mechanical heart valves). If combined, use the lowest effective aspirin dose, tighten INR monitoring, and add gastroprotection (PPI).