A quantitative, in vitro appraisal of experimental low-glucose storage solutions used for blood banking

Abstract

Red Blood Cell (RBC) transfusion has become one of the most widely utilized life-saving activities in hospitals. The most recent national report on blood banking indicates a decline in blood shortages and infections. However, the safety and efficacy of transfusion medicine are still of interest, especially for long term stored RBCs. It is well understood that stored RBCs undergo several metabolic and physical changes during the storage period, collectively known as the storage lesion, which may increase the risk of post-transfusion complications. Here, to investigate the effects of glucose on stored RBCs, three sets of normoglycemic collection and storage solutions were developed. Specifically, two factors, intracellular sorbitol accumulation and RBC-derived adenosine triphosphate (ATP) release, were quantified in this work. It is well-known that the production of sorbitol is associated with increased oxidative stress to cells. Our results reveal that RBCs produce three to five fold more sorbitol when processed in currently-approved storage solutions, while the production of sorbitol from RBCs stored in modified, normoglycemic solutions show no statistical difference to fresh blood during the first four weeks of storage. Furthermore, using a 3D-printed microfluidic device that enabled circulation of RBCs, we demonstrate that maintaining the glucose level of storage solutions between normoglycemic levels of 4–6 mM enables RBCs to release ATP at levels equal to fresh, non-stored RBCs. However, hyperglycemia impairs this RBC-derived ATP release by 50%. Combined with our previous discoveries, the work presented here strongly suggests that storing RBCs in physiological levels of glucose may be able to reduce the occurrence of the storage lesion and further diminish complications related to transfusion.