[Variable platelet response to aspirin and new therapeutic targets].
Aspirin is the first-line oral antiplatelet drug to prevent thromboembolic arterial occlusions. Aspirin irreversibly inhibits cyclooxygenase (COX) 1 involved in the platelet production of thromboxane (TX) A(2), an inducer of vasoconstriction and a platelet activating agent. Recurrent vascular events despite aspirin intake, combined with laboratory evidence of poor antiplatelet effect, suggested what has been called "aspirin resistance". For clarity's sake a real aspirin resistance would be the absence of COX1 inhibition due to intrinsic platelet factors (which has never been reported). What has been described is (expected) variability. COX1 inhibition can be insufficient to modify TX-dependent platelet behaviour. Other agonists, the production of which does not involve COX1, can stimulate TX-receptors. The antiplatelet effect of aspirin can be insufficient for pharmacokinetic or pharmacodynamic reasons, the latter being further classified as TX-dependent or not. If platelets are so reactive that responses are more TX-independent than normally, then neither aspirin nor any drugs acting on this pathway can do the job. These mechanisms should be better understood and diagnosed, and this is the prerequisite for the development of newer antiplatelet agents.
Richard
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Inserm U734 << nouvelles approches antithrombotiques >>, faculté de médecine, université de Nancy, CHU de Nancy, Nancy, France. s.richard@chu-nancy.fr
Toussaint-Hacquard
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Lecompte
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D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D000077144:Clopidogrel; D004351:Drug Resistance; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin