DEFECTIVE PLATELET-AGGREGATION IN UREMIA IS TRANSIENTLY WORSENED BY HEMODIALYSIS

Bleeding is a prominent feature of uremia and remains a significant ca use of morbidity in hemodialysis (HD)-dependent patients. To measure t he impact of the HD procedure, we performed a prospective cross-over s tudy in eight patients placed consecutively for 2-week periods each on low-flux biocompatible polymethylmethacrylate, low-flux complement-ac tivating cuprophane, and high-flux biocompatible polysulfone membranes . The primary measure of platelet function studied was shear-induced p latelet aggregation (SIPA), which has been shown to be a physiological ly relevant marker of platelet function and involves the interaction o f von Willebrand factor (vWf) with platelet membrane glycoproteins (GP ) Ib and IIb-IIIa. Flow-cytometric analysis of the surface expression of platelet membrane GP Ib and GP IIb-IIIa was performed using fluores cein isothiocyanate (FITC)-conjugated monoclonal antibodies CD42b and CD41a, respectively. Multivariate analysis did not demonstrate a stati stically significant effect of the type of dialysis membrane on platel et aggregation, calcium flux, or thromboxane B-2 production. There was a marked decrease of SIPA in HD patients (pre-HD, mean +/- SEM, 19% /- 3%) compared with normal controls (43% +/- 3%, P < 0.001), with a f urther decrease after the HD procedure (post-HD, 12% +/- 2%, P = 0.015 compared with pre-HD). This intradialytic decrease in SIPA correlated with a decrease in GP Ib (pre-HD, 385 +/- 21 mean fluorescence intens ity [MFI]; post-HD, 285 +/- 21 MFI, P = 0.0001). GP IIb-IIIa was also significantly decreased post-HD (pre-HD, 1,022 +/- 70 MFI; post-HD, 88 1 +/- 64 MFI, P = 0.03). Calcium flux and thromboxane B-2 generation i n response to shear stress were not significantly different between pr e- and post-HD samples. These studies suggest that the transient decre ase in SIPA after the HD procedure may be related to the toss of speci fic platelet receptors during HD. (C) 1995 by the National Kidney Foun dation, Inc.