“Aspirin Resistance” in Ischemic Stroke: Insights Using Short Thrombelastography

Aims 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)...

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Bibliographic Details
Published in:Journal of stroke and cerebrovascular diseases 2013-11, Vol.22 (8), p.1412-1419
Main Authors: Sambu, Nalyaka, MRCP, MD, Radhakrishnan, Ashwin, BM, BMedSCi, Englyst, Nicola, PhD, Weir, Nicolas, MRCP, MSc, MD, Curzen, Nick, PhD, FRCP
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Aspirin - therapeutic use
Aspirin resistance
Biomarkers - blood
Brain Ischemia - blood
Brain Ischemia - drug therapy
Cardiovascular
Cytokines - blood
Drug Resistance
Female
Humans
ischemic stroke
Male
Middle Aged
Neurology
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - therapeutic use
platelet function testing
Platelet Function Tests
Prospective Studies
Stroke - blood
Stroke - drug therapy
thrombelastography
Thrombelastography - methods
thromboxane B2
Thromboxane B2 - blood
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Summary:Aims 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. Methods and 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. Conclusion 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.
ISSN:1052-3057
1532-8511
DOI:10.1016/j.jstrokecerebrovasdis.2013.05.031