Red blood cells metabolome changes upon treatment with different X-ray irradiation doses
The upholding of red blood cells (RBC) quality and the removal of leukocytes are two essential issues in transfusion therapy. Leukodepletion provides optimum results, nonetheless there are cases where irradiation is recommended for some groups of hematological patients such as the ones with chronic graft-vs-host disease, congenital cellular immunodeficiency, and hematopoietic stem cell transplant recipients. The European guidelines suggest irradiation doses from 25 to 50 Gray (Gγ). We evaluated the effect of different prescribed doses (15 to 50 Gγ) of X-ray irradiation on fresh leukodepleted RBCs bags using a novel protocol that provides a controlled irradiation. Biochemical assays integrated with RBCs metabolome profile, assessed by nuclear magnetic resonance spectroscopy, were performed on RBC units supernatant, during 14 days storage. Metabolome analysis evidenced a direct correlation between concentration increase of three metabolites, glycine, glutamine and creatine, and irradiation dose. Higher doses (35 and 50 Gγ) effect on RBC mean corpuscular volume, hemolysis, and ammonia concentration are considerable after 7 and 14 days of storage. Our data show that irradiation with 50 Gγ should be avoided and we suggest that 35 Gγ should be the upper limit. Moreover, we suggest for leukodepleted RBCs units the irradiation with the prescribed dose of 15 Gγ, value at center of bag, and ranging between 13.35–15 Gγ, measured over the entire bag volume, may guarantee the same benefits of a 25 Gγ dose assuring, in addition, a better quality of RBCs.
KeywordsNMR metabolomics Ammonium X-ray irradiation RBC metabolome Bone marrow transplant Leukemia
Bone marrow transplant
Mean corpuscular volume
Nuclear magnetic resonance
Reactive oxygen species
Red blood cell
Compliance with ethical standards
The study was approved by the Arcispedale Santa Maria Nuova (ASMN)-IRCCS Ethics Committee on July 1, 2016.
Conflict of interest
The authors declare that they have no conflict of interest.
Statement of informed consent
Informed consent was obtained from all patients for being included in the study.
- 6.Qadri SM, Chen D, Schubert P, Devine DV, Sheffield WP (2017) Early γ-irradiation and subsequent storage of red cells in SAG-M additive solution potentiate energy imbalance, microvesiculation and susceptibility to stress-induced apoptotic cell death. Vox Sang 112:480–483. https://doi.org/10.1111/vox.12518 CrossRefPubMedGoogle Scholar
- 7.Szweda-Lewandowska Z, Krokosz A, Gonciarz M, Zajeczkowska W, Puchała M. (2003) Damage to human erythrocytes by radiation-generated HO• radicals: molecular changes in erythrocytes membranes. Free Rad Res 37:1137–1143, Damage to Human Erythrocytes by Radiation-generated HO• Radicals: Molecular Changes in Erythrocyte Membranes.CrossRefGoogle Scholar
- 10.Winter KM, Johnson L, Kwok M, Reid S, Alarimi Z, Wong JK, Dennington PM, Marks DC (2015) Understanding the effects of gamma-irradiation on potassium levels in red cell concentrates stored in SAG-M for neonatal red cell transfusion. Vox Sang 108:141–150. https://doi.org/10.1111/vox.12194 CrossRefPubMedGoogle Scholar
- 11.Zimmermann R, Wintzheimer S, Weisbach V, Strobel J, Zingsem J, Eckstein R (2009) Influence of prestorage leukoreduction and subsequent irradiation on in vitro red blood cell (RBC) storage variables of RBCs in additive solution saline-adenine-glucose-mannitol. Transfusion 49:75–80. https://doi.org/10.1111/j.1537-2995.2008.01920.x CrossRefPubMedGoogle Scholar
- 14.de Oliveira GC, Maia GA, Cortes VF, Santos Hde L, Moreira LM, Barbosa LA (2013) The effect of γ-radiation on the hemoglobin of stored red blood cells: the involvement of oxidative stress in hemoglobin conformation. Ann Hemat 92:899–906. https://doi.org/10.1007/s00277-013-1719-z CrossRefGoogle Scholar
- 27.Pertinhez TA, Casali E, Lindner L, Spisni A, Baricchi R, Berni P (2014) Biochemical assessment of red blood cells during storage by (1)H nuclear magnetic resonance spectroscopy. Identification of a biomarker of their level of protection against oxidative stress. Blood Transfus 12:548–556. https://doi.org/10.2450/2014.0305-13. CrossRefPubMedPubMedCentralGoogle Scholar