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Background We explored the effects of repeated plateletpheresis on the platelet P-selectin expression and soluble P-selectin (sP-selectin) concentrations in platelet donors. Methods Totally 289 platelet donors and 97 first-time whole blood (WB) donors were enrolled from the blood donor registry at the Fujian provincial blood center, China. The accumulative numbers of plateletpheresis in the last 2 y for participants were recorded, and the basal concentrations of platelet count, sP-selectin and total platelet P-selectin (pP-selectin) were determined. Results Platelet donors had significantly higher basal concentrations of sP-selectin compared to WB donors (24.12 ± 7.33 ng/mL vs. 20.74 ± 5.44 ng/mL, P < 0.0001), with no difference in platelet count and pP-selectin concentrations. Increased numbers of platelet donation were correlated with a steady increase of sP-selectin ( r = 0.18, P = 0.002). Multivariate regression analysis identified that the frequency of plateletpheresis is an independent factor for the rise of the sP-selectin concentration (t = 2.64, P = 0.009) while no association was found for pP-selectin and platelet count. Conclusions Repeated plateletpheresis could result in an increased basal concentration of sP-selectin in blood donors whereas not an alteration in the concentrations of total platelet P-selectin. It remains to be determined whether this might be a consequence of endothelial activation or platelet activation or some other phenomenon. [ABSTRACT FROM AUTHOR]