From the Guidelines
Aspirin inhibits platelet aggregation by irreversibly blocking the enzyme cyclooxygenase-1 (COX-1), which is responsible for converting arachidonic acid to thromboxane A2, a potent platelet activator and vasoconstrictor. This mechanism is supported by the most recent and highest quality study, which highlights the importance of COX-1 inhibition in preventing platelet activation and aggregation 1. The inhibition of COX-1 by aspirin is irreversible, meaning that the enzyme is permanently inactivated for the lifespan of the platelet, which is approximately 7-10 days. As a result, aspirin's antiplatelet effect begins within 30-60 minutes of ingestion at doses as low as 75-100 mg daily.
Some key points to consider when evaluating the mechanism of action of aspirin on platelet function include:
- The role of COX-1 in converting arachidonic acid to thromboxane A2, and the subsequent inhibition of this process by aspirin 1
- The irreversible nature of COX-1 inhibition by aspirin, which results in permanent inactivation of the enzyme for the lifespan of the platelet 1
- The effectiveness of low-dose aspirin (75-100 mg daily) in preventing cardiovascular events, and the potential increased bleeding risk associated with higher doses 1
Overall, the evidence suggests that aspirin's mechanism of action on platelet function is primarily related to its ability to irreversibly inhibit COX-1, which in turn reduces thromboxane A2 production and platelet activation. This makes aspirin an effective therapy for preventing cardiovascular events in high-risk patients, although it also increases bleeding risk, particularly in the gastrointestinal tract.
From the Research
Mechanism of Action of Acetylsalicylic Acid (Aspirin) on Platelet Function
- Aspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation 2, 3, 4, 5, 6
- The antiplatelet action of aspirin is due to inhibition of platelet function by acetylation of the platelet cyclooxygenase (COX) at the functionally important amino acid serine529, preventing the access of the substrate (arachidonic acid) to the catalytic site of the enzyme at tyrosine385 and resulting in an irreversible inhibition of platelet-dependent thromboxane formation 4
- Aspirin is an approximately 150- to 200-fold more potent inhibitor of the (constitutive) isoform of the platelet enzyme (COX-1) than the (inducible) isoform (COX-2) which is expressed by cytokines, inflammatory stimuli, and some growth factors 4
- Aspirin inhibits thromboxane A2 and prostaglandin formation in platelets and prostaglandin I2 (prostacyclin) in vascular cells, preventing platelet aggregation by irreversible acetylation of cyclooxygenase, a key enzyme in the arachidonic acid metabolism 3
Effects of Aspirin on Platelet Function and Thrombosis
- Aspirin prevents thrombotic events by reducing thromboxane A2 formation and platelet aggregation, and has been assessed in patients with a history of myocardial infarction, stroke, transient ischemic attack or unstable angina 3
- The optimum dose of aspirin as an antithrombotic drug can differ in different organ circulations, while 100 mg/day is sufficient for prevention of thrombus formation in the coronary circulation, higher doses may be required for the prevention of vascular events in the cerebral and peripheral circulation 4
- Aspirin is the "gold standard" antiplatelet agent for prevention of arterial thromboses, but any effective antiplatelet dose of aspirin is associated with an increased risk of bleeding 4
- The non-platelet actions of aspirin limit its antithrombotic effects, and decreasing the synthesis of anti-aggregatory PGI2 and PGD2 at non-platelet sites can lead to predicted thrombosis increase 6