DEFECTIVE PLATELET-AGGREGATION IN UREMIA IS TRANSIENTLY WORSENED BY HEMODIALYSIS

Bleeding is a prominent feature of uremia and remains a significant cause of morbidity in hemodialysis (HD)-dependent patients. To measure the impact of the HD procedure, we performed a prospective cross-over study in eight patients placed consecutively for 2-week periods each on low-flux biocompatible polymethylmethacrylate, low-flux complement-activating cuprophane, and high-flux biocompatible polysulfone membranes. The primary measure of platelet function studied was shear-induced platelet aggregation (SIPA), which has been shown to be a physiologically relevant marker of platelet function and involves the interaction of 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 fluorescein isothiocyanate (FITC)-conjugated monoclonal antibodies CD42b and CD41a, respectively. Multivariate analysis did not demonstrate a statistically significant effect of the type of dialysis membrane on platelet 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 further 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 intensity [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, 881 +/- 64 MFI, P = 0.03). Calcium flux and thromboxane B-2 generation in response to shear stress were not significantly different between pre- and post-HD samples. These studies suggest that the transient decrease in SIPA after the HD procedure may be related to the toss of specific platelet receptors during HD. (C) 1995 by the National Kidney Foundation, Inc.