A phenomenon in which the thrombus formation inhibitory effect is attenuated (large amount) or enhanced (small amount) depending on the dose of aspirin. The same drug has the opposite effect depending on the dose.
Aspirin irreversibly inhibits cyclooxygenase (COX) -1 and 2 and prostaglandin (PG) G2 and PGH2 produced from arachidonic acid by this enzyme, and their downstream products (this series). The reaction is called the arachidonic acid cascade).
Among the final products of the arachidonic acid cascade, PGI2 produced mainly in vascular endothelial cells suppresses platelet aggregation, and thromboxane (TX) A2 produced in platelets has an effect of promoting platelet aggregation. ..
Since aspirin irreversibly inhibits COX, it significantly reduces TXA2 even at low doses (∵ platelets do not have nuclei and cannot synthesize new enzymes), but PGI2 is well compensated for at low doses of aspirin. (∵ Because vascular endothelial cells synthesize new COX).
Therefore, low dose (about 81-100 mg / day for adults) aspirin increases the PGI2 / TXA2 ratio and works prophylactically against thrombosis and embolus.
However, the cost of PGI2 cannot keep up with high-dose administration, and the inhibitory effect on platelet aggregation is diminished.