Platelet receptor shedding: An in vitro study in shock-related platelet functional impairment.

BACKGROUND: Early platelet dysfunction is a key component of trauma-induced coagulopathy. Studies have suggested that excess catecholamine following shock conditions may be implicated through proteolytic shedding of key platelet surface receptors. This study investigates the impact of epinephrine exposure on platelet receptor shedding and its subsequent effects on platelet activation, aggregation, and adhesion in an in vitro model. METHODS: Whole blood samples were exposed to increasing concentrations of epinephrine for 5 and 30 minutes. Enzyme-linked immunosorbent assay was then used to quantify levels of key platelet receptors. Platelet activation was assessed via flow cytometry using platelet activation complex-1 staining. Platelet aggregation to collagen-coated microfluidic channels and platelet adhesion to human umbilical vein endothelial cell-coated microfluidic channels were measured by fluorescence. Matrix metalloproteinase and a disintegrin and metalloproteinase 17 activities were measured using fluorometric assays. RESULTS: Epinephrine exposure significantly increased shedding of all measured platelet surface receptors in a dose- and time-dependent manner versus control (no epinephrine). These changes were accompanied by significant increases in matrix metalloproteinase and a disintegrin and metalloproteinase 17 activity. Platelet activation, adhesion, and aggregation were also significantly decreased with epinephrine exposure compared with control, especially at higher epinephrine concentrations and with longer exposure times. CONCLUSION: Epinephrine exposure was shown to increase platelet receptor shedding in a time- and concentration-dependent manner. This correlated with an increase in metalloproteinase activity, suggesting a possible mechanistic link. Increased platelet receptor shedding was also associated with impaired platelet adherence and aggregation in microfluidic devices. These findings support the role of catecholamine excess in early platelet dysfunction following shock and present possible therapeutic targets for future studies.