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Storage lesion indicators change in an orderly fashion, namely, by following donor-related prestorage attributes. These correlations are illustrated for the first time in "prestorage versus storage" biologic networks, which might help determine the best candidates for in vivo biomarkers of storage quality and provide deeper insight into the apparently complex donor variation effect on the RBC storage lesion.

UA exhibits a storability biomarker potential. Intrinsic variability in plasma UA levels might be related to the interdonor variability observed in the storage capacity of RBCs. A model for the antioxidant effect of UA during the RBC storage is currently proposed.

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BACKGROUND Previous investigations in leukoreduced units of red blood cells (RBCs) in mannitol additive solution revealed the close association of uric acid (UA) levels in vivo with the susceptibility of RBCs to storage lesion markers. In this study, we examined whether UA has a similar correlation with the capability of RBCs to cope with the oxidative provocations of storage under different conditions, namely, in CPDA‐1 and in the absence of leukoreduction. STUDY DESIGN AND METHODS The UA‐dependent antioxidant capacity of the supernatant was measured in nonleukoreduced units of RBCs in CPDA (n = 47). The possible effect of UA variability on the storage lesion profile was assessed by monitoring several physiologic properties of RBCs and supernatant, including cell shape, reactive oxygen species, and size distribution of extracellular vesicles, in units exhibiting the lowest or highest levels of UA activity (n = 16) among donors, throughout the storage period. RESULTS In stored RBC units, the UA‐dependent antioxidant activity of the supernatant declined as a function of storage duration but always in strong relation to the UA levels in fresh blood. Contrary to units of poor‐UA activity, RBCs with the highest levels of UA activity exhibited better profile of calcium‐ and oxidative stress–driven modifications, including a significant decrease in the percentages of spherocytes and of 100‐ to 300‐nm‐sized vesicles, typically associated with the exovesiculation of stored RBCs. CONCLUSION The antioxidant activity of UA is associated with donor‐specific differences in the performance of RBCs under storage in nonleukoreduced CPDA units.