Does aspirin (acetylsalicylic acid) inhibit platelet function?

Aspirin's Effect on Platelet Function

Yes, aspirin definitively inhibits platelet function through irreversible inactivation of cyclooxygenase-1 (COX-1) within platelets. 1

Mechanism of Action

• Aspirin permanently acetylates the serine residue at position 529 (Ser529) within the polypeptide chain of platelet prostaglandin H-synthase (COX-1) 1, 2
• This irreversible inhibition prevents the formation of thromboxane A2 (TXA2), a potent vasoconstrictor and platelet aggregator 1
• The antiplatelet effect is achieved through a "hit-and-run" mechanism with a short-lived active moiety, limiting extra-platelet effects 1
• Platelet inhibition is fully present with low doses of aspirin (75-100 mg daily) 2, 3
• The effect persists for the entire lifespan of the affected platelets (7-10 days) due to their inability to synthesize new proteins 2

Clinical Significance

• Aspirin's antiplatelet effect reduces cardiovascular events by 25-30% in high-risk patients 1
• It is effective in both primary and secondary prevention of cardiovascular events 1
• The antiplatelet effect is evident clinically as a prolonged bleeding time 1
• Aspirin is considered the "gold standard" antiplatelet agent for prevention of arterial thromboses 3

Dosing Considerations

• Low-dose aspirin (75-100 mg daily) is sufficient to achieve complete inhibition of platelet COX-1 2
• Higher doses do not provide additional antiplatelet benefits but increase bleeding risk 1, 3
• Some evidence suggests that 75 mg/day may be less effective than 325 mg/day in preventing graft occlusion after coronary bypass surgery 1
• Enteric-coated formulations may have reduced bioavailability, potentially affecting antiplatelet efficacy 1

Aspirin Resistance

• Despite therapy, approximately 10-20% of aspirin-treated patients experience recurrent vascular events within 5 years 1
• "Aspirin resistance" refers to either:
  • Biochemical resistance: inability to inhibit platelet aggregation in laboratory tests 1
  • Clinical resistance: occurrence of cardiovascular events despite aspirin therapy 1
• Prevalence estimates range from 5-60%, depending on the population studied and assay used 1
• Patients with laboratory evidence of aspirin resistance have a significantly higher risk (hazard ratio 3.12) of future cardiovascular death, MI, or stroke 1

Mechanisms of Aspirin Resistance

• Multiple factors can affect platelet aggregation despite aspirin therapy:
  • Patient factors: posture, time of day, exercise, serum cholesterol levels 1
  • Cigarette smoking stimulates platelet aggregation and blunts aspirin's effect 1
  • Drug interactions: NSAIDs may block aspirin's access to COX-1 1
  • Genetic variability in COX-1 may modulate response to aspirin 4
• Increased platelet turnover can lead to newly formed platelets with COX-2 expression, which is 150-fold less sensitive to aspirin than COX-1 1
• Systemic oxidative inflammation may maintain platelet function despite COX-1 inhibition 5

Clinical Implications

• Aspirin is a cornerstone of treatment for atherothrombotic diseases 2
• The irreversible nature of aspirin's effect has implications for surgical procedures, with recovery of platelet function typically requiring 5-7 days after discontinuation 2
• Dual antiplatelet therapy (aspirin plus P2Y12 inhibitor) provides more comprehensive inhibition of platelet activation pathways 2
• Aspirin's antiplatelet effect cannot be dissociated from an increased risk of bleeding 3

In summary, aspirin definitively inhibits platelet function through irreversible acetylation of COX-1, preventing thromboxane A2 formation. This effect is permanent for the lifespan of the affected platelets and is achieved with low doses. While highly effective for most patients, a subset may exhibit aspirin resistance through various mechanisms, potentially limiting its clinical benefit.