Erythrocyte concentrates (ECs) stored for transfusion purposes still represent a lifesaving solution in a wide series of clinically occurring circumstances, especially for traumatized and perioperative patients. However, concerns still arise and persist as to whether current criteria for collection and storage of ECs might actually represent the best case scenario or there might rather be still room for improvement. In particular, the prolonged storage of EC has been associated with the accumulation of a wide series of storage lesions, either reversible (metabolism) or irreversible (protein and morphology). Independent laboratories have contributed to propose alternative strategies, among which is the introduction of oxygen removal treatments to ECs. Convincing biochemical and preliminary clinical evidences have been produced about the benefits derived from the introduction of this practice. We, hereby, propose a rapid, efficient, and time-effective strategy for blood deoxygenation which might fit in current EC production chain. The proposed strategy resulted in the complete deoxygenation of red blood cell hemoglobin ( ？mmHg). A preliminary small-scale study about the application of the present method resulted in reduced hemolysis, decreased vesiculation, and limited alterations to the red blood cell morphology, as gleaned from flow cytometry and scanning electron microscopic analyses. Further in-depth and larger-scale investigations are encouraged. 1. Introduction Erythrocyte concentrates (ECs) are still the most widely transfused blood-derived therapeutic worldwide, as many million units of blood are collected, and million units of RBCs are administered to millions of patients every year [1, 2]. Currently, accepted European Council guidelines indicate that ECs may be stored for up to 42 days under controlled conditions before transfusion [3]. Nevertheless, recent retrospective and controversial studies have brought about concerns on the suitability of longer stored EC units for transfusion purposes [4, 5]. It has indeed been stressed that the risk of exposure to long-stored red blood cells (RBCs) is exacerbated when dealing with certain categories of recipients, such as traumatized, postoperative, and critically ill patients [5]. However, it should be worth mentioning that early results from randomized double-blind clinical prospective trials have not hitherto indicated any statistically significant disadvantage of the administration of longer stored units in comparison to fresher blood [6, 7]. While the likelihood of untoward effects related to the
References
[1]
J. R. Hess, “Red cell storage,” Journal of Proteomics, vol. 73, no. 3, pp. 368–373, 2010.
[2]
A. D'Alessandro, G. Liumbruno, G. Grazzini, and L. Zolla, “Red blood cell storage: the story so far,” Blood Transfusion, vol. 8, no. 2, pp. 82–88, 2010.
[3]
European Directorate for the Quality of Medicines, “Guide to the preparation, use and quality assurance of blood components,” Recommendation no. 95, 15-16th Edition. Council of Europe, 2011.
[4]
C. G. Koch, L. Li, D. I. Sessler et al., “Duration of red-cell storage and complications after cardiac surgery,” The New England Journal of Medicine, vol. 358, no. 12, pp. 1229–1239, 2008.
[5]
J. L. Vincent, C. Lelubre, and M. Piagnerelli, “Association between duration of storage of transfused red blood cells and morbidity and mortality in adult patients: myth or reality?” Transfusion, vol. 49, no. 7, pp. 1384–1394, 2009.
[6]
D. A. Fergusson, P. Hébert, D. L. Hogan et al., “Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial,” JAMA, vol. 308, no. 14, pp. 1443–1451, 2012.
[7]
W. A. Flegel, “Fresh blood for transfusion: how old is too old for red blood cell units?” Blood Transfusion, vol. 10, no. 3, pp. 247–251, 2012.
[8]
E. Bennett-Guerrero, T. H. Veldman, A. Doctor et al., “Evolution of adverse changes in stored RBCs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 43, pp. 17063–17068, 2007.
[9]
A. D'Alessandro, G. M. D'Amici, S. Vaglio, and L. Zolla, “Time-course investigation of SAGM-stored leukocyte-filtered erythrocyte concentrates: from metabolism to proteomics,” Haematologica, vol. 97, no. 1, pp. 107–115, 2012.
[10]
C. R. Valeri and N. M. Hirsch, “Restoration in vivo of erythrocyte adenosine triphosphate, 2,3-diphosphoglycerate, potassium ion, and sodium ion concentrations following the transfusion of acid-citrate-dextrose-stored human red blood cells,” The Journal of Laboratory and Clinical Medicine, vol. 73, no. 5, pp. 722–733, 1969.
[11]
O. Rubin, D. Crettaz, J. D. Tissot, and N. Lion, “Microparticles in stored red blood cells: Submicron clotting bombs?” Blood Transfusion, vol. 8, no. 3, pp. s31–s38, 2010.
[12]
G. J. C. G. M. Bosman, E. Lasonder, M. Luten et al., “The proteome of red cell membranes and vesicles during storage in blood bank conditions,” Transfusion, vol. 48, no. 5, pp. 827–835, 2008.
[13]
G. M. D'Amici, S. Rinalducci, and L. Zolla, “Proteomic analysis of RBC membrane protein degradation during blood storage,” Journal of Proteome Research, vol. 6, no. 8, pp. 3242–3255, 2007.
[14]
S. Rinalducci, G. M. D'Amici, B. Blasi, S. Vaglio, G. Grazzini, and L. Zolla, “Peroxiredoxin-2 as a candidate biomarker to test oxidative stress levels of stored red blood cells under blood bank conditions,” Transfusion, vol. 51, no. 7, pp. 1439–1449, 2011.
[15]
M. Antonelou, A. Kriebardis, K. Stamoulis, L. Margaritis, I. Trougakos, and I. Papassideri, “Secretory apolipoprotein J/Clusterin is an integral component of human erythrocytes and a novel biomarker of vesiculation and senescence in vivo and in stored red cells,” in Proceedings of the 31st International Congress of the International Society of Blood Transfusion (ISBT '10), vol. 99, p. 213, Vox Sanquinis, Berlin, Germany, 2010.
[16]
R. Chaudhary and R. Katharia, “Oxidative injury as contributory factor for red cells storage lesion during twenty eight days of storage,” Blood Transfusion, vol. 10, no. 1–4, pp. 59–62, 2011.
[17]
D. Shemin and D. Rittenberg, “The life span of the human red blood cell,” The Journal of Biological Chemistry, vol. 166, no. 2, pp. 627–636, 1946.
[18]
J. Racek, R. Herynková, V. Holecek, Z. Jerábek, and V. Sláma, “Influence of antioxidants on the quality of stored blood,” Vox Sanguinis, vol. 72, no. 1, pp. 16–19, 1997.
[19]
L. J. Dumont, T. Yoshida, and J. P. AuBuchon, “Anaerobic storage of red blood cells in a novel additive solution improves in vivo recovery,” Transfusion, vol. 49, no. 3, pp. 458–464, 2009.
[20]
T. Yoshida, J. P. AuBuchon, L. J. Dumont et al., “The effects of additive solution pH and metabolic rejuvenation on anaerobic storage of red cells,” Transfusion, vol. 48, no. 10, pp. 2096–2105, 2008.
[21]
T. Yoshida and S. S. Shevkoplyas, “Anaerobic storage of red blood cells,” Blood Transfusion, vol. 8, no. 4, pp. 220–236, 2010.
[22]
W. H. Forbes and F. J. Roughton, “The equilibrium between oxygen and haemoglobin: I. The oxygen dissociation curve of dilute blood solutions,” The Journal of Physiology, vol. 71, no. 3, pp. 229–260, 1931.
[23]
S. C. Glauser and R. E. Forster 2nd, “pH dependence of the oxyhemoglobin dissociation curve at high oxygen tension,” Journal of Applied Physiology, vol. 22, no. 1, pp. 113–116, 1967.
[24]
P. Astrup, K. Engel, J. W. Severinghaus, and E. Munson, “The influence of temperature and pH on the dissociation curve of oxyhemoglobin of human blood,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 17, no. 6, pp. 515–523, 1965.
[25]
T. Elssner, M. Kostrzewa, T. Maier, and G. Kruppa, “Microorganism identification based on MALDI-TOF-MS fingerprints,” NATO Science for Peace and Security Series A, pp. 99–113, 2011.
[26]
M. Harboe, “A method for determination of hemoglobin in plasma by near-ultraviolet spectrophotometry,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 11, no. 1, pp. 66–70, 1959.
[27]
O. Rubin, J. Delobel, M. Prudent et al., “Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation,” Transfusion, 2012.
[28]
A. Givan, “Flow cytometry,” in Methods in Molecular Biology: Flow Cytometry Protocols, T. S. Hawley and R. G. Hawley, Eds., Humana Press, Totowa, NJ, USA, 2011.
[29]
C. F. H？gman, H. L？f, and H. T. Meryman, “Storage of red blood cells with improved maintenance of 2,3-bisphosphoglycerate,” Transfusion, vol. 46, no. 9, pp. 1543–1552, 2006.
[30]
J. K. Tusa and H. He, “Critical care analyzer with fluorescent optical chemosensors for blood analytes,” Journal of Materials Chemistry, vol. 15, no. 27-28, pp. 2640–2647, 2005.
[31]
B. Blasi, A. D'Alessandro, N. Ramundo, and L. Zolla, “Red blood cell storage and cell morphology,” Transfusion Medicine, vol. 22, no. 2, pp. 90–96, 2012.
[32]
A. D'Alessandro, F. Gevi, and L. Zolla, “Red blood cell metabolism under prolonged anaerobic storage,” Molecular BioSystems, 2013.
[33]
F. Gevi, A. D'Alessandro, S. Rinalducci, and L. Zolla, “Alterations of red blood cell metabolome during cold liquid storage of erythrocyte concentrates in CPD-SAGM,” Journal of Proteomics, vol. 76, pp. 168–180, 2012.
