Ex Vivo Thrombocyte Function and Its Response to NO/Sildenafil in Patients Undergoing Hemodialysis

体外血小板功能及其对血液透析患者NO/西地那非的反应

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Abstract

Background: Coagulation disorders, including both bleeding and thrombotic complications, are common in patients undergoing hemodialysis (HD). Here, we aimed to characterize platelet function in patients undergoing hemodialysis three times per week, compared to healthy controls. Methods: Platelet function was assessed using the Multiplate analyzer (Roche), which is based on multiple electrode impedance aggregometry. Platelet aggregation was induced using adenosine diphosphate (ADP), and the area under the curve (AUC) served as the primary endpoint. In addition, platelet counts and C-reactive protein (CRP) levels were measured. To further evaluate nitric oxide (NO)-mediated inhibition of platelet aggregation, blood samples were incubated with the NO donor, sodium nitroprusside (SNP), and the phosphodiesterase 5A (PDE5A) inhibitor, sildenafil. Results: A total of 60 patients undergoing HD and 67 healthy controls were included in the analysis. Patients receiving HD treatment had significantly lower platelet counts compared to healthy controls (226.9 ± 53.47 vs. 246.7 ± 47.21 G/L, p = 0.029). Platelet aggregation was markedly reduced in patients undergoing HD compared to controls (462.0 ± 266.54 vs. 644.5 ± 254.44 AU × min, p < 0.001) with a significant correlation for platelet count (r = 0.42, p = 0.001) and systemic inflammation as indicated by CRP levels (r = 0.28, p = 0.035). Following SNP and sildenafil administration, inhibition of platelet aggregation remained more pronounced in patients undergoing HD. However, the change in platelet aggregation after SNP/sildenafil treatment did not differ significantly between the groups. Conclusions: Patients undergoing HD exhibit altered platelet function, indicated by reduced aggregation and platelet counts, as well as an association with systemic inflammation. Multiple electrode impedance aggregometry appears to be a feasible method for detecting platelet function alterations in patients receiving HD treatment. Responsiveness to NO donors was preserved in patients undergoing HD. Further studies are needed to identify the underlying mechanisms, particularly the role of NO signaling in platelet dysfunction in patients undergoing HD.

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