Platelet Hyperreactivity to Submaximal Epinephrine: Biologic and Genetic Correlates.

Platelet hyperreactivity constitutes an important thrombotic risk factor; however, standardized methods for its measurement are lacking. We recently reported that aggregometry using a submaximal concentration of epinephrine (0.4 μM in citrated platelet-rich plasma) identifies individuals with in vitro platelet hyperreactivity; this hyperreactivity was reproducible on multiple occasions over long periods of time (up to 3 years). To better understand this aberrant reactivity, we studied in a larger group of subjects (n=404) the association between healthy individuals’ platelet reactivity to epinephrine and their platelet phenotype as measured by other functional and biochemical assays. Fourteen percent (n=56) of our study cohort showed a hyperreactive response (> 60% aggregation) to 0.4 μM epinephrine; the remainder showed a minimal response (see figure). Subjects with hyperreactivity to epinephrine were more likely to exhibit hyperaggregability to other agonists (ADP, arachidonic acid, collagen, collagen-related peptide and ristocetin; p GNB3 ) encoding the beta-3 subunit of G proteins (p 2A -adrenergic receptor. Aggregometry using submaximal concentrations of epinephrine thus identifies a global hyperreactive platelet phenotype and may be useful in settings where platelet hyperreactivity bears special relevance - for example, in populations of patients at risk for thrombosis. Our findings also suggest that the physiologic determinants of platelet hyperreactivity in response to different types of stimulation may share common signaling pathways, possibly involving G protein-coupled receptors and increased GP IIb-IIIa expression.