title: Is arachidonic acid stimulation really a test for the response to aspirin? Time to think again?
abstract: Platelets play a key role in pathogenesis of atherothrombosis. Activated platelets initiate thrombus formation. Antiplatelet therapy (APT) modifies these properties. APT involves aspirin. The existence of 'aspirin resistance' is reported in many populations with cardiovascular disease. The prevalence of this phenomenon is highly variable, affecting more than 50% of patient subgroups in some papers. Areas covered: This review describes the prevalence of 'aspirin resistance', analyses why there is so much apparent variation and addresses whether the commonly used tests of aspirin response are in fact accurately assessing its functional performance. The clinical consequences if arachidonic acid(AA)-mediated assays do not accurately assess the functional performance of aspirin could be important. Expert commentary: Two important issues arise, firstly, that it can no longer be considered robust to use AA-induced platelet activation as a true diagnostic test of functional response to aspirin. It is clear that the output from PFT using AA as an agonist are not even a surrogate for the pharmacological activity of aspirin. Secondly, current data raise important and clinically relevant questions about, how AA stimulation induces clotting in individuals in whom aspirin is effective at its COX-1 target. The evidence indicates at least one recruitable, COX-1-independent pathway that is associated with vascular inflammation.
authors.affiliation: a Wessex Cardiothoracic Centre , University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Olechowski
authors.affiliation: a Wessex Cardiothoracic Centre , University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ashby
authors.affiliation: a Wessex Cardiothoracic Centre , University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Mariathas
authors.affiliation: a Wessex Cardiothoracic Centre , University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Vikram
authors.initials: V
authors.lastname: Khanna
authors.affiliation: a Wessex Cardiothoracic Centre , University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: a Wessex Cardiothoracic Centre , University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Curzen
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests / Q000379:methods*; D015203:Reproducibility of Results; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control
chemical_list: D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D001241:Aspirin
keywords: Aspirin; aspirin resistance; high on platelet reactivity; platelet function assay; stent thrombosis