Residual cyclooxygenase-1 activity and epinephrine reduce the antiplatelet effect of aspirin in patients with acute myocardial infarction

Antonio Moscardó; María Teresa Santos; María Paz Fuset; Miguel Ruano; Juana Vallés

doi:10.1160/TH10-08-0550

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(04): 663-669
DOI: 10.1160/TH10-08-0550

Platelets and Blood Cells

Schattauer GmbH

Residual cyclooxygenase-1 activity and epinephrine reduce the antiplatelet effect of aspirin in patients with acute myocardial infarction

Authors

Antonio Moscardó

¹Research Center, University Hospital La Fe, Valencia, Spain
María Teresa Santos^*

¹Research Center, University Hospital La Fe, Valencia, Spain
María Paz Fuset

²Intensive Care Unit, University Hospital La Fe, Valencia, Spain
Miguel Ruano

²Intensive Care Unit, University Hospital La Fe, Valencia, Spain
Juana Vallés^*

¹Research Center, University Hospital La Fe, Valencia, Spain

Abstract

Summary

Aspirin treatment is essential in patients with acute myocardial infarction (AMI) to block platelet thromboxane (TXA)2 synthesis. Epinephrine is known to enhance platelet reactivity induced by other agonists and to be elevated in patients with AMI due to stress. Our objective was to study the influence of epinephrine on platelet TXA₂ synthesis in patients treated with aspirin for AMI at early onset (within 48 hours) and the potential biochemical mechanisms involved in the functional response. Washed platelets from 45 patients with AMI and 10 aspirin-free controls were stimulated with arachidonic acid (AA) or AA + epinephrine, and aggregation and TXA₂ synthesis were evaluated. Full platelet aggregation was recorded in 8/45 patients (18%) with a partial TXA₂ inhibition (86%) vs. the aspirin-free controls. Platelets from the remaining 37 patients did not aggregate to AA and had TXA₂ inhibition >95%. However, when platelets were simultaneously stimulated with AA + epinephrine, in 25/37 patients a large intensity of aggregation (73%) was observed and a 5.5-fold increase in TXA₂ synthesis, although this remained residual (<5% of aspirin-free controls). This residual-TXA₂ was critical in the functional response, as demonstrated by the complete inhibition by TXA₂ receptor blockade or additional aspirin in vitro. The phosphatidylinositol-3-kinase activity and the cytosolic calcium levels participated in this platelet response elicited by a receptor cooperation mechanism, while the Rho/p160^ROCK pathway or the blockade of the ADP receptors (P2Y1, P2Y12) were without effect. Residual-cyclooxygenase –1 activity and epinephrine enhance TXA₂-dependent platelet function, which may reduce the clinical benefit of aspirin in patients with AMI.

Keywords

Platelets - aspirin - thromboxane A₂ - epinephrine - acute myocardial infarction

Full Text

References

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