Increased platelet expression of FcGammaRIIa and its potential impact on platelet reactivity in patients with end stage renal disease

BACKGROUND: Increased platelet reactivity has been implicated in cardiovascular disease – the major cause of death in patients with end stage renal disease (ESRD). FcGammaRIIA is a component of glycoprotein VI and Ib-IX-V that mediate activation of platelets by collagen and von Willebrand factor. To determine whether expression of FcGammaRIIA impacts platelet reactivity we quantified its expression and platelet reactivity in 33 patients with ESRD who were undergoing hemodialysis. METHODS: Blood samples were obtained from patients immediately before hemodialysis and before administration of heparin. Platelet expression of FcGammaRIIA and the activation of platelets in response to low concentrations of convulxin (1 ng/ml, selected to mimic effects of collagen), thrombin (1 nM), adenosine diphosphate (ADP, 0.2 uM), or platelet activating factor (PAF, 1 nM) were determined with the use of flow cytometry in samples of whole blood anticoagulated with corn trypsin inhibitor (a specific inhibitor of Factor XIIa). RESULTS: Patients were stratified with respect to the median expression of FcGammaRIIA. Patients with high platelet expression of FcGammaRIIA exhibited 3-fold greater platelet reactivity compared with that in those with low expression in response to convulxin (p < 0.01) and 2-fold greater activation in response to thrombin, ADP, and PAF (p < 0.05 for each). For each agonist, expression of FcGammaRIIA correlated modestly but positively with platelet reactivity. The strongest correlation was with thrombin-induced activation (r = 0.6, p < 0.001). CONCLUSION: Increased platelet reactivity in response to low concentrations of diverse agonists is associated with high expression of FcGammaRIIA and may contribute to an increased risk of thrombosis in patients with ESRD.