The heritability of hemolysis in stored human red blood cells

Abstract

Background The transfusion of red blood cells (RBCs) with maximum therapeutic efficacy is a major goal in transfusion medicine. One of the criteria used in determining stored RBC quality is end of storage hemolysis. Between donors, a wide range of hemolysis is observed under identical storage conditions. Here, a potential mechanism for this wide range is investigated. We hypothesize that the magnitude of hemolysis is a heritable trait. Also, we investigated correlations between hemolysis and RBC metabolites; this will establish pathways influencing hemolysis as future targets for genetic analysis. Study Design and Methods Units of RBCs from identical and non-identical twins were collected and stored under standard conditions for 56 days. Hemolysis, ATP, and total glutathione were measured throughout storage. Non-targeted metabolic analyses were performed on RBCs that had been stored for 28 days. Heritability was determined by comparing values between identical and non-identical twins. Results Hemolysis was found to be heritable (mean >45 %) throughout the storage period. Correlations were observed between hemolysis and metabolites from the amino acid, sugar, and purine metabolism, lipid metabolism and transport, and glycolysis pathways. Three metabolites also exhibited heritability (> 20%). No correlation was found with ATP or total glutathione. Conclusion The susceptibility of RBCs to lysis during storage is partly determined by inheritance. We have also uncovered several pathways that are candidate targets for future genome wide association studies. These findings will aid in the design of better storage solutions and the development of donor screening tools that minimize hemolysis during storage.

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

“…27,28 Our larger study shows that these same metabolic pathways are significantly impacted by the formulation of storage additives in a manner that goes beyond the direct impact of the unique components in the AS (e.g. mannitol vs citrate in AS-1 vs AS-3).…”

Red blood cell storage in additive solution‐7 preserves energy and redox metabolism: a metabolomics approach

“…This effect promoted better preservation of DPG and redox poise (higher levels of PPP intermediates and stability and/or increased total GSH pools) in AS‐7 in comparison to AS‐3 RBCs especially during the first week of storage. Recent publications proposed preliminary correlations between AS‐3 metabolic profiles and a key transfusion outcome, hemolysis . To further the relevance of metabolomics analyses in transfusion medicine, future studies should investigate whether significant correlations exist between metabolite levels and other markers of storage quality and transfusion outcomes, such as morphology, hemolysis, and 24‐hour in vivo survival …”

Quality Assessment of Established and Emerging Blood Components for Transfusion

“…Recently it has come to light that donor factors might also influence the in vitro quality of stored red blood cell products [256–259]. Analysis of quality control data from national blood banking agencies suggests that storage-associated hemolysis in stored RCCs is dependent on donor characteristics such as sex, age, ethnicity, and heritable genetic traits [256, 260–264]. …”