title: "Aspirin resistance" in ischemic stroke: insights using short thrombelastography.
abstract: OBJECTIVE
  Aspirin achieves its antithrombotic effect through inactivation of cyclo-oxygenase (COX)-1, thereby preventing generation of thromboxane (TX)A2 from arachidonic acid (AA). The reported prevalence of aspirin "resistance" varies significantly and is usually based on platelet function tests (PFTs) that use AA-induced platelet reactivity as a surrogate measure of the effect of aspirin, rather than specific assessment of its effect on its therapeutic target (ie, COX-1 inhibition). The reported rates are not only assay specific but also condition specific, with particularly high rates (up to 70%) previously reported in the stroke population. We investigated whether pharmacological responses to aspirin can be reliably determined from a functional test of AA-induced whole-blood clotting.
  
  
  RESULTS
  A prospective study included 35 patients admitted with ischemic stroke and commenced on 300 mg aspirin. AA-induced whole-blood clotting was measured using short thrombelastography, a previously extensively validated near-patient PFT. Serum TXB2 and inflammatory biomarkers were also measured. The prevalence of apparent aspirin resistance measured using AA was high (range from 49% to 67%). However, serum [TXB2] was consistently low, thereby confirming adequate inhibition of COX-1 by aspirin. Mean inflammatory biomarker levels were elevated throughout.
  
  
  CONCLUSIONS
  This study demonstrates that although COX-1 activity is adequately and consistently suppressed by aspirin in stroke patients, this effect is not reliably indicated by whole-blood clotting in response to AA. These data help to explain why the reported prevalence of aspirin resistance in stroke from studies employing AA-induced platelet reactivity is high and cast doubt on the veracity of such reports.
authors.affiliation: Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Nalyaka
authors.initials: N
authors.lastname: Sambu
authors.forename: Ashwin
authors.initials: A
authors.lastname: Radhakrishnan
authors.forename: Nicola
authors.initials: N
authors.lastname: Englyst
authors.forename: Nicolas
authors.initials: N
authors.lastname: Weir
authors.forename: Nick
authors.initials: N
authors.lastname: Curzen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D020521:Stroke / Q000097:blood / Q000188:drug therapy*; D013916:Thrombelastography / Q000379:methods*; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D001241:Aspirin
keywords: Aspirin resistance; ischemic stroke; platelet function testing; thrombelastography; thromboxane B2