Aspirin resistance

Abstract

In their Review, Graeme Hankey and John Eikelboom (Feb 18, p 606)1Hankey GJ Eikelboom JW Aspirin resistance.Lancet. 2006; 367: 606-617Summary Full Text Full Text PDF PubMed Scopus (506) Google Scholar define laboratory resistance to aspirin as “the failure of aspirin to inhibit platelet thromboxane A2 production or inhibit tests of platelet function that are dependent on platelet thromboxane production”. Two studies2Pulcinelli FM Riondino S Celestini A et al.Persistent production of platelet thromboxane A2 in patients chronically treated with aspirin.J Thromb Haemost. 2005; 3: 2784-2789Crossref PubMed Scopus (64) Google Scholar, 3Maree AO Curtin RJ Dooley M et al.Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease.J Am Coll Cardiol. 2005; 46: 1258-1263Summary Full Text Full Text PDF PubMed Scopus (182) Google Scholar in patients treated with long-term aspirin seem to support such a definition, but they deserve careful consideration. These studies showed persistent platelet thromboxane A2 formation in some patients. In-vitro addition of aspirin resulted in a significant decrease in platelet thromboxane A2 formation. Addition of an antagonist of thromboxane A2 inhibited platelet aggregation, suggesting that residual thromboxane A2 production was functionally relevant.2Pulcinelli FM Riondino S Celestini A et al.Persistent production of platelet thromboxane A2 in patients chronically treated with aspirin.J Thromb Haemost. 2005; 3: 2784-2789Crossref PubMed Scopus (64) Google Scholar This incomplete COX-1 inhibition in patients treated with long-term aspirin could result from genetic variability of COX-1 or from reduced aspirin bioavailability.2Pulcinelli FM Riondino S Celestini A et al.Persistent production of platelet thromboxane A2 in patients chronically treated with aspirin.J Thromb Haemost. 2005; 3: 2784-2789Crossref PubMed Scopus (64) Google Scholar The relation between genetic variability of COX-1 and aspirin activity was investigated by Maree and colleagues,4Maree AO Curtin RJ Chubb A et al.Cyclooxygenase-1 haplotype modulates platelet response to aspirin.J Thromb Haemost. 2005; 3: 2340-2345Crossref PubMed Scopus (207) Google Scholar who found a significant haplotype association with platelet thromboxane A2 generation and suggested that the promoter −842G allele could contribute significantly to aspirin insensitivity. Data on aspirin bioavailability are few and require further investigation. A crucial limitation of the studies that explored the relation between aspirin intake and platelet thromboxane A2 is related to the fact that aspirin compliance was only indirectly documented. Tantry and colleagues5Tantry US Bliden KP Gurbel PA Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation.J Am Coll Cardiol. 2005; 46: 1705-1709Summary Full Text Full Text PDF PubMed Scopus (297) Google Scholar studied 223 patients on long-term aspirin for coronary heart disease who claimed to be aspirin compliant. Arachidonic-acid-induced platelet aggregation was measured in all patients and was less than 10% in all but seven, who admitted later to being non-compliant. In these seven patients, readministration of aspirin along with accurate analysis of their compliance decreased arachidonic-acid-induced platelet aggregation to less than 10%. Since these data raise doubts about the existence of aspirin resistance, future studies must take into account aspirin compliance before concluding that patients are resistant to aspirin because of persistent platelet production of thromboxane A2. We declare that we have no conflict of interest.