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

BMC Nephrology

Rob Fijnheer¹  Mark Roest³  Leonie A Boven¹  Carlo A Gaillard²  Loes Cornelissen³  Daisy Walter³  Rosa L de Jager¹  Esther R van Bladel³ 

[1]Department of Internal Medicine and Laboratory Medicine, Meander Medical Center, Utrechtseweg 160, 3800, BM, Amersfoort, The Netherlands

[2]Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands

[3]Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands

关键词: End-stage renal disease;    Cardiorenal syndrome;    Haemodialysis;    Platelet activation;   

Others  :  1083084
DOI  :  10.1186/1471-2369-13-127

 received in 2012-05-08, accepted in 2012-08-22,  发布年份 2012

【 摘 要 】

Background

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 this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease.

Methods

Platelet 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.

Results

We 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.

Conclusion

In 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.

【 授权许可】

   
2012 van Bladel et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Fried LF, Shlipak MG, Crump C, Bleyer AJ, Gottdiener JS, Kronmal RA, Kuller LH, Newman AB: Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 2003, 41:1364-1372.
• [2]Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004, 351:1296-1305.
• [3]Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW: Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003, 108:2154-2169.
• [4]Kaw D, Malhotra D: Platelet dysfunction and end-stage renal disease. Semin Dial 2006, 19:317-322.
• [5]Jalal DI, Chonchol M, Targher G: Disorders of hemostasis associated with chronic kidney disease. Semin Thromb Hemost 2010, 36:34-40.
• [6]Moal V, Brunet P, Dou L, Morange S, Sampol J, Berland Y: Impaired expression of glycoproteins on resting and stimulated platelets in uraemic patients. Nephrol Dial Transplant 2003, 18:1834-1841.
• [7]Noris M, Remuzzi G: Uremic bleeding: closing the circle after 30years of controversies? Blood 1999, 94:2569-2574.
• [8]Rios DR, Carvalho MG, Lwaleed BA, Silva AC Se, Borges KB, Dusse LM: Hemostatic changes in patients with end stage renal disease undergoing hemodialysis. Clin Chim Acta 2010, 411:135-139.
• [9]Collins AJ, Li S, Gilbertson DT, Liu J, Chen SC, Herzog CA: Chronic kidney disease and cardiovascular disease in the Medicare population. Kidney Int Suppl 2003, 87:S24-S31.
• [10]Henry RM, Kostense PJ, Bos G, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD: Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study. Kidney Int 2002, 62:1402-1407.
• [11]Muntner P, He J, Hamm L, Loria C, Whelton PK: Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol 2002, 3:745-753.
• [12]Nitta K: Pathogenesis and therapeutic implications of cardiorenal syndrome. Clin Exp Nephrol 2011, 15:187-194.
• [13]Aggarwal A, Kabbani SS, Rimmer JM, Gennari FJ, Taatjes DJ, Sobel BE, Schneider DJ: Biphasic effects of hemodialysis on platelet reactivity in patients with end-stage renal disease: a potential contributor to cardiovascular risk. Am J Kidney Dis 2002, 40:315-322.
• [14]Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 1976, 16:31-41.
• [15]van der Putten K, Jie KE, Emans ME, Verhaar MC, Joles JA, Cramer MJ, Velthuis BK, Meiss L, Kraaijenhagen RJ, Doevendans PA, Braam B, Gaillard CA: Erythropoietin treatment in patients with combined heart and renal failure: objectives and design of the EPOCARES study. J Nephrol 2010, 23(4):363-368.
• [16]Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K, ESC Committee for Practice Guidelines (CPG): ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail 2008, 10:933-989.
• [17]van Bladel ER, Roest M, de Groot PG, Schutgens RE: Up-regulation of platelet activation in hemophilia A. Haematologica 2011, 96:888-895.
• [18]Kyrle PA, Stockenhuber F, Brenner B, Gössinger H, Korninger C, Pabinger I, Sunder-Plassmann G, Balcke P, Lechner K: Evidence for an increased generation of prostacyclin in the microvasculature and an impairment of the platelet alpha-granule release in chronic renal failure. Thromb Haemost 1988, 60:205-208.
• [19]Schoorl M, Bartels PCM, Gritters M, Fluitsma D, Musters R, Nubé MJ: Electron microscopic observation in case of platelet activation in a chronic haemodialysis subject. Hematol Rep 2011, 3:e15.
• [20]Zwaginga JJ, IJsseldijk MJ, Beeser-Visser N, De Groot PG, Vos J, Sixma JJ: High von Willebrand factor concentration compensates a relative adhesion defect in uremic blood. Blood 1990, 75:1498-1508.
• [21]Casserly LF, Dember LM: Thrombosis in end-stage renal disease. Semin Dial 2003, 16:245-256.
• [22]Palmer SC, Di Micco L, Razavian M, Craig JC, Perkovic V, Pellegrini F, Copetti M, Graziano G, Tognoni G, Jardine M, Webster A, Nicolucci A, Zoungas S, Strippoli GF: Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease. A systematic review and meta-analysis. Ann Intern Med 2012, 156:445-459.
• [23]Zwaginga JJ: Hemodialysis, erythropoietin and megakaryocytopoiesis: factors in uremic thrombocytopathy and thrombophilia. J Thromb Haemost 2004, 2(8):1272-1274.
• [24]Stumpf C, Lehner C, Eskafi S, Raaz D, Yilmaz A, Ropers S, Schmeisser A, Ludwig J, Daniel WG, Garlichs CD: Enhanced levels of CD154 (CD40 ligand) on platelets in patients with chronic heart failure. Eur J Heart Fail 2003, 5:629-637.