Age-Related Modulations in Erythrocytes under Blood Bank Conditions

Abstract

<b><i>Background:</i></b> During storage of erythrocytes, storage lesions are formed that reduce the safety and efficacy of the stored blood. Thus, there is a need to understand the changes that occur during storage. Most studies have focused on storage of a mixed population of erythrocytes. The aim of this study is to analyze the changes in young and old erythrocytes over the course if storage. <b><i>Materials and Methods:</i></b> Blood was collected from the blood bank at the Kempegowda Institute of Medical Sciences (KIMS) Hospital (Bengaluru, India) and stored for 35 days in CPDA-1 at 4°C. Every 5 days, erythrocytes were separated based on the blood’s age using a Percoll-BSA gradient. Young and old erythrocytes obtained were used for analysis of the following oxidative stress (OS) markers: hemoglobin (Hb), hemolysis, mechanical fragility, antioxidant enzymes (superoxide dismutase and catalase [CAT]), superoxides, sialic acid, glutamic oxaloacetate transaminase (GOT), glucose, plasma membrane redox system (PMRS), total antioxidant capacity-cupric ion reducing antioxidant capacity assay (TAC<sub>CUPRAC</sub>), lactate dehydrogenase (LDH), lipid peroxidation products (malondialdehyde [MDA] and conjugate dienes), and protein oxidation products (advanced oxidation protein products and protein sulfhydryls). <b><i>Result:</i></b> Young cells had higher amounts of Hb, sialic acid, GOT, LDH, TAC<sub>CUPRAC</sub>, CAT, and superoxides compared to old cells. Old cells, however, had higher PMRS and MDA levels with respect to young cells. <b><i>Discussion:</i></b> Young cells could endure OS during storage more efficiently than old cells. In conclusion, the efficacy of stored blood depends on the ratio of young cells in the population. This study highlights the prospects of storing young erythrocytes for a prolonged shelf life of blood.

Donor‐dependent aging of young and old red blood cell subpopulations: Metabolic and functional heterogeneity

“…These progressive morphologic and metabolic changes in RBCs after processing (washing alone or Percoll separation) and throughout storage were accompanied by changes in RBC quality characteristics including increased hemolysis and decreased Hb‐p50 and deformability, which is consistent with previously reported results 34,62–64 . The significantly increased hemolysis and rigidity and decreased elongation in the group of washed but unseparated RCCs show the high sensitivity of RBCs to the secondary effect of washing and storage methods on processed RBCs.…”

“…According to previously reported data, 32,34,49 young RBCs lose their unique structural characteristics by Days 21 to 25 of storage and a notable shift to a sphere‐shaped morphology occurs after 28 days of hypothermic storage. Therefore, it was anticipated that many of the structural differences between young and old RBCs would be negligible over storage time due to their chronological aging, especially in in vitro conditions where removal of senescent RBCs through phagocytosis is unavailable.…”

“…57,58 These progressive morphologic and metabolic changes in RBCs after processing (washing alone or Percoll separation) and throughout storage were accompanied by changes in RBC quality characteristics including increased hemolysis and decreased Hb-p50 and deformability, which is consistent with previously reported results. 34,[62][63][64] of senescent RBCs within a RCC will presumptively have higher accumulation of side products of aging/lysis that undoubtedly affect the quality of the whole RCC unit. Other studies have discussed the impact of donor age and sex on both the quality characteristics of RCCs during in vitro storage 22,25,28,65 and the transfusion efficacy, [66][67][68][69] with an increased risk of mortality due to sex-mismatched transfusions.…”

“…29 The concept of RCCs as a heterogeneous population of RBCs of varying age that exhibit different structural, functional, and metabolic properties is increasingly being described. [30][31][32][33][34] This study proposes that donor characteristics such as age, sex, and number of previous blood donations have implications on the distribution of young and old RBC subpopulations. This maturity-related RBC heterogeneity may in turn impact the RCC storage lesion and therefore the quality of transfused products.…”

“…RCCs containing a greater proportion of old RBCs may have increased lysis products contributing to an overall decrease in cellular recovery, oxygen delivery, and metabolic stability of RCCs during in vitro hypothermic storage 29 . The concept of RCCs as a heterogeneous population of RBCs of varying age that exhibit different structural, functional, and metabolic properties is increasingly being described 30–34 …”