Abstract
BackgroundAspirin resistance established by different laboratory methods is still a debated problem. Using COX1 specific methods no aspirin resistance was detected among healthy volunteers. Here we tested the effect of chronic aspirin treatment on platelets from patients with stable coronary artery disease. The expression of COX2 mRNA in platelets and its influences on the effect of aspirin was also investigated.MethodsOne hundred and forty four patients were enrolled in the study. The direct measurement of COX1 acetylation was carried out by monoclonal antibodies specific to acetylated and non-acetylated COX1 (acCOX1 and nacCOX1) using Western blotting technique. Arachidonic acid (AA) induced TXB2 production by platelets was measured by competitive immunoassay. AA induced platelet aggregation, ATP secretion and VerifyNow Aspirin Assay were also performed. COX2 and COX1 mRNA expression in platelets were measured in 56 patients by RT-qPCR.ResultsIn 138 patients only acCOX1 was detected, in the remaining six patients nacCOX1 disappeared after a compliance period. AA induced TXB2 production by platelets was very low in all patients including the 6 patients after compliance. AA induced platelet aggregation, secretion and with a few exceptions the VerifyNow Assay also demonstrated the effect of aspirin. Smoking, diabetes mellitus and inflammatory conditions did not influence the results. The very low amount of COX2 mRNA detected in 39 % of the investigated platelets did not influence the effect of aspirin.ConclusionsNo aspirin resistance was detected among patients with stable coronary artery disease. COX2 expression in platelets did not influence the effect of aspirin.
Highlights
Aspirin resistance established by different laboratory methods is still a debated problem
It has been shown that the method is highly sensitive and could detect as low as 2.5 % of the total platelet COX1 in non-acetylated form [11], i.e. more than 97.5 % of platelet COX-1 was acetylated as the consequence of long term aspirin treatment
According to sample size calculations the lack of aspirin resistance in all of the 144 patients indicated that aspirin is effective in more than 98 % of patients with stable coronary artery disease
Summary
Aspirin resistance established by different laboratory methods is still a debated problem. The ineffectiveness of aspirin in protecting an individual from acute vascular events is often considered “aspirin resistance” such cases are very likely related to the fact that aspirin inhibits effectively and selectively only one out of several pathways leading to platelet activation [9, 10] It fails to inhibit platelet activation induced by strong agonists, like thrombin or high dose of collagen and only partially inhibits ADP induced platelet aggregation. In a recent study we developed monoclonal antibodies reacting with acetylated and non-acetylated COX1 (acCOX1 and nacCOX1, respectively) for the first time, and utilizing these antibodies a highly specific and sensitive method that detects 2.5 % of platelet nacCOX1 was developed [11] Using this method that measures COX1 acetylation by aspirin directly, no aspirin resistance was found among 108 healthy volunteers taking 100 mg enteric-coated aspirin daily for 7 days. Complete inhibition of TXB2 formation during coagulation of whole blood was observed in 24 healthy volunteers after 7 days of aspirin treatment [13]
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