Abstract
Red blood cell transfusion is a life-saving intervention, and storage is a logistic necessity to make ~110 million units available for transfusion every year worldwide. However, storage in the blood bank is associated with a progressive metabolic decline, which correlates with the accumulation of morphological lesions, increased intra- and extra-vascular hemolysis upon transfusion, and altered oxygen binding/off-loading kinetics. Prior to storage, red blood cells are suspended in nutrient formulations known as additive solutions to prolong cellular viability. Despite a thorough expansion of knowledge regarding red blood cell biology over the past few decades, only a single new additive solution has been approved by the Food and Drug Administration this century, owing in part to the limited capacity for development of novel formulations. As a proof of principle, we leveraged a novel high-throughput metabolomics technology as a platform for rapid data-driven development and screening of novel additive solutions for blood storage under both normoxic and hypoxic conditions. To this end, we obtained leukocyte-filtered red blood cells (RBCs) and stored them under normoxic or hypoxic conditions in 96 well plates (containing polyvinylchloride plasticized with diethylhexylphthalate to concentrations comparable to full size storage units) in the presence of an additive solution supplemented with six different compounds. To inform this data-driven strategy, we relied on previously identified metabolic markers of the RBC storage lesion that associates with measures of hemolysis and post-transfusion recovery, which are the FDA gold standards to predict stored blood quality, as well as and metabolic predictors of oxygen binding/off-loading parameters. Direct quantitation of these predictors of RBC storage quality were used here—along with detailed pathway analysis of central energy and redox metabolism—as a decision-making tool to screen novel additive formulations in a multiplexed fashion. Candidate supplements are shown here that boost-specific pathways. These metabolic effects are only in part dependent on the SO2 storage conditions. Through this platform, we anticipate testing thousands of novel additives and combinations thereof in the upcoming months.
Highlights
Despite these advancements in red blood cells (RBCs) storage strategies, there is room for improvement in blood storage (Yoshida et al, 2019), as storage in the blood bank promotes the accumulation of a series of biochemical and morphological changes to Red blood cell (RBC) that impact their energy and redox metabolism (Rogers et al, 2021), protein membrane integrity, morphology (D’alessandro et al, 2012), functionality in vitro, in animal models in vivo (Hod et al, 2010), and clearance upon transfusion (Roussel et al, 2021)
Leukocyte-filtered RBCs were collected from 12 healthy donor volunteers and added to either standard pediatric size DEHPcontaining bags or in 96 well plate format containing AS-3, prior to storage under refrigerated conditions and weekly sampling for metabolomics (Figure 1A)
After confirming that storage in 96 well plate format is comparable to storage in the bag, we set out to determine whether RBCs could be stored at
Summary
Blood transfusion is the most common in-hospital procedure (Pfuntner et al, 2013) and a critical life-saving intervention for 3.5–5 million Americans annually. Red blood cell (RBC) storage in the blood bank is a critical procedure that makes it logistically feasible to collect and store ~110 millions of units of blood donated in 13,282 centers across 176 countries around the world every year (George, 2018) Despite these advancements in RBC storage strategies, there is room for improvement in blood storage (Yoshida et al, 2019), as storage in the blood bank promotes the accumulation of a series of biochemical and morphological changes to RBCs that impact their energy and redox metabolism (Rogers et al, 2021), protein membrane integrity (e.g., band 3 fragmentation; Issaian et al, 2021), morphology (D’alessandro et al, 2012), functionality in vitro (e.g., decreased 2,3-diphosphoglycerate and oxygen off-loading capacity; Tsai et al, 2010; Donovan et al, 2021), in animal models in vivo (Hod et al, 2010), and clearance upon transfusion (Roussel et al, 2021). This loss of potency may even be more marked in non-autologous, non-healthy recipients, such as in the case of sickle cell patients (Kozanoglu and Ozdogu, 2018), where a pro-inflammatory environment could promote erythrophagocytosis of transfused red cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
