Sensitivity to Epinephrine Determines Platelet Hyperreactivity in Myocardial Infarction under Antiplatelet Therapy

Abstract

Aim: To investigate the role of platelet adrenoreactivity in development of hyperreactive platelet phenotype in patients with myocardial infarction receiving antiplatelet therapy. Study Design: Cohort prospective study. Place and Duration of Study: Histology Department of Donetsk National medical university; Institute of Emergent and Rehabilitation Medicine, Donetsk, Ukraine, between June 2011 and September 2013. Methodology: The study was carried out on 36 patients with acute ST-elevation MI receiving double antiplatelet treatment. After assessment of epinephrine (5 µM) induced aggregation two groups of patients were identified: with high (1st group, with aggregation more than 40%) and low (2nd group, aggregation less than 40%) adrenoreactivity. Within both groups platelets’ reaction to the main agents (ADP (5 mkM), collagen (5mkg/ml), ristocetin (0.5mg/ml); thrombin (1U/ml)), was measured. Since a mixture of agonists in low concentration is present at the site of coronary arteries occlusion, subthreshold concentrations of agonists were used in addition to EC50 in order to analyze their potentiating effect on aggregation. 10 healthy volunteers were taken as a control group. The results were analyzed using MedCalc software. Results: 75% (27) of patients with MI on double antiplatelet therapy developed hyperreactivity to epinephrine. Comparison of platelet reactivity among the patients with high and low adrenoreactivity showed that hypere adrenoreactivity phenomenon was associated with higher platelet response to ADP, as well as to adhesive agents (ristocetin and collagen). Whereas subthreshold concentration did not exhibit much potentiating effect among the patients with low initial adrenoreactivity, hyper adrenoreactive patients exhibited rather powerful potentiation of effects of ADP and epinephrine. Conclusion: Adrenoreactivity plays an important role in the responsiveness to different agonists and could be a mechanism of tolerance/resistance to antiplatelet therapy among the patients with MI.