Defective platelet aggregation in uremia is transiently worsened by hemodialysis

Abstract

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 loss of specific platelet receptors during HD.