An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies

Abstract

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high-energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long-stored RBCs and promote the rapid clearance of up to one-fourth of long-stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects.

Experiment study and FEM simulation on erythrocytes under linear stretching of optical micromanipulation

“…Finally the change of 14-18 days becomes slow again. These results imply that proteins of the membrane cytoskeleton and the lipid bilayer have decomposed partially in the process of storage, 24 which resulted in the change of cell membrane thickness, and the weakness of bending resistance of membrane.…”

A self-filling microfluidic device for noninvasive and time-resolved single red blood cell experiments

“…Time-resolved analysis of single RBCs exposed to external stimuli will provide important insights into their fundamental biophysical properties like flickering of the membrane 10 as well as biomedical questions regarding the disease progression in malaria 12 or in-vitro aging of RBCs during storage in blood banks. 44 …”

Biochemistry of storage lesions of red cell and platelet concentrates: A continuous fight implying oxidative/nitrosative/phosphorylative stress and signaling

“…To some extent, hypothermic biopreservation leads to lower the above-mentioned diffusion barriers, thus promoting intracellular NO reactions. These physical barriers are regulated by RBC morphology, size and surface area, properties that are known to change during blood storage [4]. In particular, as storage time progresses, geometry of the RBCs tends to become more spherical thereby having a smaller surface area to volume ratio [23].…”

“…They are found spanning several cellular compartments (including cytoskeleton, membrane surface and cytosol) leading to a progressive damage in cell structure and function with consequent adverse clinical outcomes. Storage lesions have been shown to be associated with several physiological activities such as cytoskeletal reorganization, membrane dynamics, derangement of metabolism, activation of signaling cascades, protein translation, control of cell homeostasis and death [2][3][4].…”

“…While the contribution of oxidative stress in developing storage lesions is more clear (especially in the case of RBC storage) and extensively documented [3,4], the investigation of the protein phosphorylation-mediated signaling pathways in stored RBC and PLT concentrates have attracted attention only in the last years [5,6].…”