The red blood cell (RBC) storage lesion is a multi-parametric response that occurs during storage at 4°C, but its impact on transfused patients remains unclear. In studies of the RBC storage lesion, the temperature transition from cold storage to normal body temperature that occurs during transfusion has received limited attention. We hypothesized that multiple deleterious events might occur in this period of increasing temperature. We show dramatic alterations in several properties of therapeutic blood units stored at 4°C after warming them to normal body temperature (37°C), as well as febrile temperature (40°C). In particular, the intracellular content and redox state of nicotinamide adenine dinucleotide phosphate [NADP(H)] were directly affected by post-storage incubation at 37°C, as well as by pro-oxidant storage conditions. Modulation of the NADPH-producing pentose phosphate pathway, but not the prevention of hemoglobin autoxidation by conversion of oxyhemoglobin to carboxyhemoglobin, provided protection against storage-induced alterations in RBCs, demonstrating the central role of NADPH in mitigating increased susceptibility of stored RBCs to oxidative stress. We propose that assessing RBCs oxidative status after restoration of body temperature provides a sensitive tool to detect storage-related alterations, and has the potential to improve the quality of stored RBCs for transfusion.
Aline Roch, Nicholas J. Magon, Jessica Maire, Cacang Suarna, Anita Ayer, Sophie Waldvogel, Beat. A. Imhof, Mark J. Koury, Roland Stocker, Marc Schapira