Reasons for aspirin resistance.

Dear Sirs, The term “aspirin resistance” (1) has been used to describe a number of different phenomena, including inability of aspirin to: (i) protect against cardiovascular events despite its regular intake; (ii) to affect various laboratory tests, reflecting platelet activity. Indeed, there is a good evidence to indicate that there are subpopulations which do not respond to antithrombotic actions of aspirin in various laboratory tests. This question was recently addressed in Thrombosis and Haemostasis by P. Henry and his colleagues (2) and discussed in an accompanying editorial by M. Lordkipanidze (3). The possible explanations, given by these authors, include: lack of compliance, deficient aspirin absorption, enhanced platelet turnover and genetic predisposition. To these factors I would add hypercholesterolaemia (4). Blunting of aspirin action in hypercholesterolaemia might be explained by (i) alterations in lipid-protein matrix that render their membrane proteins less accessible for acetylation by aspirin and (ii) changes in composition and structure of plasma lipoproteins that diminish the chance of aspirin to interact with protrombin. Treatment with statins depresses blood clotting, probably decreasing expression of tissue factor (5), and might abolish to some extent, aspirin resistance. Since in the Henry et al. study one third of patients were “hyperlipidaemic”, an investigation of a possible relationship between hypercholesterolaemia and aspirin resistance seems warranted. Another predisposing factor could be a hypercoagulable state after myocardial infarction and unstable angina. Such a state follows for months – up to a year – after acute myocardial infarction (6) or unstable angina (7) and is associated with depressed sensitivity to antithrombotic agents (8), including aspirin. Finally, evidence has accumulated (9) to support a genetic association between the PLA1/A2 genetic polymorphism in the glycoprotein IIIa platelet receptor and antithrombotic action of aspirin (10–12).