Role of Platelet Surface Receptor Abnormalities in the Bleeding and Thrombotic Diathesis of Uremic Patients on Hemodialysis and Peritoneal Dialysis

Abstract

Patients with chronic renal failure suffer from bleeding diathesis and a tendency to accelerated atherosclerosis. Altered platelet function plays a well defined role in the hemorrhagic complications of these patients and has a probable impact on atherothrombotic disease in uremia. In this study we investigated the expression of platelet surface receptors, the glycoprotein GPIb (receptor for von Willebrand Factor(vWF) and GPIIb/IIIa (receptor for fibrinogen) in patient with chronic renal failure in pre-dialysis status, under hemodialysis and peritoneal dialysis treatment, in order to assess the impact of the abnormal receptorial status of uremic platelets on the clinical manifestations of hemostatic alterations in uremic patients. Thirty-seven normal healthy subjects (controls = Group A), 18 patients with mild chronic renal failure (creatinine = 1.8 +/- 0.5 mg% - Group B), 15 patients with advanced renal failure (creatinine = 5.4 +/- 2. 1 mg% - Group C), 18 hemodialysis patients (Group D) and 11 peritoneal dialysis patients (Group E) were included in the study. The expression of platelet surface receptors GPIb and GPIIb/IIIa was investigated with monoclonal antibodies CD42 and CD41 (Immunotech, Marseille, France) and a FACScan flowcytometer (Becton-Dickinson, USA). Mean values of GPIb glycoprotein (mean flow +/- SD) were: group A = 48.14 +/- 9.31; group B = 40.48 +/- 8.18 (p < 0.005); group C = 34.05 +/- 7.55 (p < 0.0005) versus group A; p = 0.025 versus group B); group D = 34.51 +/- 7.22 (p < 0.0005 versus group A; p = 0.025 group B and p = ns versus group C); group E = 26.34 +/- 4.06 (p < 0.0005 versus group A, p < 0.0005 versus group B, p < 0.005 versus groups C and D). Mean values of glycoprotein GPIIb/IIIa were: group A = 375.32 +/- 90.58; group B = 398.48 +/- 54.26 (p = ns); group C = 426.86 +/- 52.78 (p < 0.025 versus group A; p = ns versus group B); group D = 425.17 +/- 75.03 (p < 0.025 versus group A; p = ns versus groups B and C); group E = 336.39 +/- 43.26 (p = ns versus group A; p < 0.005 versus group B, p < 0.0005 versus group C and p < 0.001 versus group D). Our data confirm the receptorial defect of glycoprotein GPIb (the receptor for vWF) on the surface of uremic platelets: a negative correlation between serum creatinine and the expression of glycoprotein GPIb was found. The defect was not corrected by hemodialysis and/or peritoneal dialysis. Hemodialysis and peritoneal dialysis have a different impact on the expression of GPIIb/IIIa glycoprotein (the receptor for vWF): peritoneal dialysis seems to have a more favourable effect by restoring normal values of the expression of this membrane integrine. Theoretically the data could be correlated to the better biocompatibility of the peritoneal dialysis and to more favorable clinical behaviour in terms of accelerated atherosclerosis and athero-thrombotic complications in the uremic patients with end stage renal disease. Finally the abnormalities of platelet surface receptors may play a main role in the hemostatic alterations of uremic patients.