Abstract
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.
Similar content being viewed by others
Abbreviations
- BMT:
-
Bone marrow transplant
- GvHD:
-
Graft-versus-host disease
- MCV:
-
Mean corpuscular volume
- NMR:
-
Nuclear magnetic resonance
- ROS:
-
Reactive oxygen species
- RBC:
-
Red blood cell
References
Leitman SF, Holland PV (1985) Irradiation of blood products. Indications and guidelines. Transfusion 25:293–300
Janatpour K, Denning L, Nelson K, Betlach B, Mackenzie M, Holland P (2005) Comparison of X-ray vs gamma irradiation of CPDA-1 red cells. Vox Sang 89:215–219. https://doi.org/10.1111/j.1423-0410.2005.00699.x
Goker H, Haznedaroglu IC, Chao NJ (2001) Acute graft-vs-host disease: pathobiology and management. Exp Hematol 29:259–277
Lee SJ, Vogelsang G, Flowers ME (2003) Chronic graft-versus-host disease. Biol Blood Marrow Transplant 9:215–233. https://doi.org/10.1053/bbmt.2003.50026
Anderson K (2003) Broadening the spectrum of patient groups at risk for transfusion-associated GVHD: implications for universal irradiation of cellular blood components. Transfusion 43:1652–1654
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
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.
Abuja PM, Albertini R (2001) Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clin Chim Acta 306:1–17
Patel RM, Roback JD, Uppal K, Yu T, Jones DP, Josephson CD (2015) Metabolomics profile comparisons of irradiated and nonirradiated stored donor red blood cells. Transfusion 55:544–552. https://doi.org/10.1111/trf.12884
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
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
Moreira OC, Oliveira VH, Benedicto LB, Nogueira CM, Mignaco JA, Fontes CF, Barbosa LA (2008) Effects of γ-irradiation on the membrane ATPases of human erythrocytes from transfusional blood concentrates. Ann Hemat 87:113–119. https://doi.org/10.1007/s00277-007-0378-3
Maia GAS, Cortes VF, Ribeiro RIMDA, Mignaco JA, de Lima Santos H, Fontes CF, Barbosa LA (2014) Could Na, K-ATPase play a role in potassium leakage from irradiated erythrocytes? Clin Chim Acta 433:58–61. https://doi.org/10.1016/j.cca.2014.02.025
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
Maia GAS, de Oliveira Renó C, Medina JM, Silveira AB, Mignaco JA, Atella GC, Cortes VF, Barbosa LA, Santos H de L (2014) The effect of gamma radiation on the lipid profile of irradiated red blood cells. Ann Hemat 93:753–760. https://doi.org/10.1007/s00277-013-1944-5
Leitner GC, Neuhauser M, Weigel G, Kurze S, Fischer MB, Höcker P (2001) Altered intracellular purine nucleotides in gamma-irradiated red blood cell concentrates. Vox Sang 81:113–118
Adams F, Bellairs G, Bird AR, Oguntibeju OO (2015) Biochemical storage lesions occurring in non irradiated and irradiated red blood cells: a brief review. Biomed Res Int 2015:968302. https://doi.org/10.1155/2015/968302
Xu D, Peng M, Zhang Z, Dong G, Zhang Y, Yu H (2012) Study of damage to red blood cells exposed to different doses of γ-ray irradiation. Blood Transfus 10:321–330. https://doi.org/10.2450/2012.0076-11.
Al Zahrani K, Al-Swaidan HA (2017) Nanostructural changes in the cell membrane of gamma-irradiated red blood cells. Indian J Hematol Blood Transfus 33:109–115. https://doi.org/10.1007/s12288-016-0657-z
Krokosz A, Koziczak R, Gonciarz M, Szweda-Lewandowska Z. (2006) Study of the effect of dose-rate on radiation-induced damage to human erythrocytes. Radiation Phys Chem 75:98–105. doi.org/10.1016/j.radphyschem.2005.03.013.
Bontadini A, Tazzari TL, Manfroi S, Tassi C, Conte R (2002) Apoptosis in leukodepleted packed red blood cells. Vox Sang 83:35–41
Schmid I, Krall WJ, Uittenbogaart CH, Braun J, Giorgi JV (1992) Dead cell discrimination with 7-amino actinomycin D in combination with dual color immunofluorescence in single laser flow cytometry. Cytometry 13:204–208
Chan LL-Y, McCulley KJ, Kessel SL (2017) Assessment of cell viability with single-, dual-, and multi-staining methods using image cytometry. In Cell Viability Assays, Chap 3:27–41
Dodd B, Vetter RJ (2009) Replacement of 137Cs irradiators with x-ray irradiators. Health Phys 96:S27–S30. https://doi.org/10.1097/01.HP.0000334555.78657.bc
Vandana S, Shaiju VS, Sharma SD, Mhatre S, Shinde S, Chourasiya G, Mayya YS (2011) Dosimetry of gamma chamber blood irradiator using Gafchromic EBT film. Appl Radiat Isot 69:130–135. https://doi.org/10.1016/j.apradiso.2010.08.018
Han V, Serrano K, Devine DV (2010) A comparative study of common techniques used to measure haemolysis in stored red cell concentrates. Vox Sang 98:116–123. https://doi.org/10.1111/j.1423-0410.2009.01249.x
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.
Pertinhez TA, Casali E, Zambianchi L, Spisni A, Baricchi R (2018) Statistical validation of 1H NMR protocol vs standard biochemical assay in quality control of RBC packed units. J Pharm Biomed Anal 147:485–492. https://doi.org/10.1016/j.jpba.2017.06.024
Pelszynski MM, Moroff G, Luban NL, Taylor BJ, Quinones RR (1994) Effect of X-ray irradiation of red blood cell units on T-cell inactivation as assessed by limiting dilution analysis: implications for preventing transfusion-associated graft-versus-host disease. Blood 83:1683–1689
Akahoshi M, Takanashi M, Masuda M, Yamashita H, Hidano A, Hasegawa K, Kasajima T, Shimizu M, Motoji T, Oshimi K et al (1992) A case of transfusion-associated graft-versus-host disease not prevented by white cell-reduction filters. Transfusion 32(2):169–172
Luban NL, Drothler D, Moroff G, Quinones R (2000) Irradiation of platelet components: inhibition of lymphocyte proliferation assessed by limiting-dilution analysis. Transfusion 40(3):348–352
Mathai J (2005) Irradiated blood components. Indian J Med Res 122(5):371–373
Wegener S, Marschall M, Schnabl J, Kleine H, Freund M (2000) White cell subsets in filtered red blood cell concentrates. Transfus Sci 23(1):29–32
Rider JR, Want EJ, Winter MA, Turton JR, Pamphilon DH, Nobes P (2000) Differential leucocyte subpopulation analysis of leucodepleted red cell products. Transfus Med 10(1):49–58
Pertinhez TA, Casali E, Baroni F, Berni P, Baricchi R, Spisni A (2016) A comparative study of the effect of leukoreduction and pre-storage leukodepletion on red blood cells during storage. Front Mol Biosci 3:13. https://doi.org/10.3389/fmolb.2016.00013
Antosik A, Czubak K, Gajek A, Marczak A, Glowacki R, Borowczyk K, Zbikowska HM (2015) Influence of prestorage irradiation on the oxidative stress markers, membrane integrity, size and shape of the cold stored red blood cells. Transfus Med Hemotherapy 42:140–148
Ku CP, Passow H (1980) Creatine and creatinine transport in old and young human red blood cells. Biochim Biophys Acta-Biomembranes 600:212–227
Davies SM, Szabo E, Wagner JE, Ramsay NK, Weisdorf DJ (1996) Idiopathic hyperammonemia: a frequently lethal complication of bone marrow transplantation. Bone Marrow Transplant 17:1119–1125
Tse N, Cederbaum S, Glaspy JA (1991) Hyperammonemia following allogeneic bone marrow transplantation. Am J Hematol 38:140–141
Espinos J, Rifon J, Pérez-Calvo J, Nieto Y (2006) Idiopathic hyperammonemia following high-dose chemotherapy. Bone Marrow Transplant 37:899. https://doi.org/10.1038/sj.bmt.1705346
Apushkin M, Das A, Joseph C, Leung EK, Yeo KT, Baron JM, Baron BW (2013) Reducing the risk of hyperammonemia from transfusion of stored red blood cells. Transfus Apher Sci 49:459–462. https://doi.org/10.1016/j.transci.2013.05.002
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The study was approved by the Arcispedale Santa Maria Nuova (ASMN)-IRCCS Ethics Committee on July 1, 2016.
ᅟ
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.
Electronic supplementary material
ESM 1
(DOCX 127 kb)
Rights and permissions
About this article
Cite this article
Baroni, F., Marraccini, C., Merolle, L. et al. Red blood cells metabolome changes upon treatment with different X-ray irradiation doses. Ann Hematol 97, 1909–1917 (2018). https://doi.org/10.1007/s00277-018-3386-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-018-3386-6