Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro

Esther R Van Bladel,Rob Fijnheer,Leonie A Boven,Loes Cornelissen,Rosa L De Jager,Daisy Walter,Carlo A Gaillard,Mark Roest

doi:10.1186/1471-2369-13-127

Abstract

BackgroundIn patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease.MethodsPlatelet reactivity was measured using flow cytometric analysis. Platelets in whole blood were triggered with different concentrations of agonists (TRAP, ADP, CRP). Platelet activation was quantified with staining for P-selectin, measuring the mean fluorescence intensity. Area under the curve and the concentration of half-maximal response were determined.ResultsWe studied 23 patients with chronic kidney disease (9 patients with cardiorenal failure and 14 patients with end stage renal disease) and 19 healthy controls. Expression of P-selectin on the platelet surface measured as mean fluorescence intensity was significantly less in chronic kidney disease patients compared to controls after maximal stimulation with TRAP (9.7 (7.9-10.8) vs. 11.4 (9.2-12.2), P = 0.032), ADP (1.6 (1.2-2.1) vs. 2.6 (1.9-3.5), P = 0.002) and CRP (9.2 (8.5-10.8) vs. 11.5 (9.5-12.9), P = 0.004). Also the area under the curve was significantly different. There was no significant difference in half-maximal response between both groups.ConclusionIn this study we found that patients with chronic kidney disease show reduced platelet reactivity in response of ADP, TRAP and CRP compared to controls. These results contribute to our understanding of the aberrant platelet function observed in patients with chronic kidney disease and emphasize the significance of using functional whole blood platelet activation assays.

Highlights

In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests
Pre-versus-post dialysis To rule out an activating effect of the hemodialysis procedure on baseline platelet activation we studied platelet activation before and immediate after dialysis
The aim of this study was to investigate the relation between platelet function and kidney failure in patients with end stage renal disease and cardiorenal syndrome using a flow cytometer based, functional platelet assay

Summary

Introduction

In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In chronic kidney disease both bleeding and thrombotic complications are observed. Platelet dysfunction is thought to be caused by the action of uremic toxins, anemia, increased nitric oxide production, von Willebrand factor abnormalities and the use of van Bladel et al BMC Nephrology 2012, 13:127 http://www.biomedcentral.com/1471-2369/13/127 medication like aspirin, non-steroidal anti-inflammatory drugs and β-lactam antibiotics [4,6,7,8]. Besides an increased bleeding risk, a variety of thrombotic complications are observed in patients with chronic renal failure, including coronary heart disease, cerebrovascular disease, peripheral vascular disease and heart failure. Already in mild to moderate chronic kidney disease an increased risk of cardiovascular events and higher mortality have been reported [1,2,9,10,11,12]

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