Conformational disorders of RBC membranes during long-term storage
V. A. Sergunova,
A. N. Kuzovlev,
A. D. Onufrievich,
V. A. Inozemtsev,
O. E. Gudkova,
E. A. Sherstyukova https://doi.org/10.35754/0234-5730-2022-67-2-181-192
Abstract
Introduction. Packed red blood cells (pRBCs) are the most required component of blood used for transfusion. Storage of erythrocytes in blood bank conditions causes a disruption of the molecular structure of long-stored pRBC membranes. This “disruption” can affect the quality and safety of transfused red blood cells.
Aim — to analyze the dynamics of pathological changes in the morphology, nanostructure, cytoskeleton network, and mechanical properties of RBC membranes during long-term storage of pRBCs, and the relationship of these changes with storage time.
Materials and methods. Hermetic bags of pRBCs with anticoagulant CPD in resuspending solution SAGM were stored for 42 days at +4 °С. Samples were taken on days 3, 12, 19, 21, 24, 28, 35, and 42 of storage and images of morphology, nanostructure, and cytoskeleton were obtained by atomic force microscopy. Young’s modulus was used to assess the stiffness of native cell membranes using atomic force spectroscopy.
Results. During storage of pRBCs, their cell morphology changed. After 20–24 days of storage an irreversible transformation of discocytes into echinocytes, spheroequinocytes and other cell forms occurred. It was found that during storage of pRBCs, topological defects in the form of domains with grains appeared on the surface of RBC membranes, the configuration of the cytoskeleton network transformed structurally, and the Young’s modulus increased.
Conclusions. During long-term storage of pRBCs (up to 42 days, 4 °С, CPD/SAGM) the molecular structure of RBCs undergoes irreversible disorders. These changes occur, as a rule, after 20–24 days of storage.
About the Authors
V. A. Sergunova
“V.A. Negovsky Scientific Research Institute of General Reanimatology” of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation
Russian Federation
Viktoria A. Sergunova, Cand. Sci. (Biol.), Head of the Laboratory of Biophysics of Cell Membranes under Critical State
107031, Moscow
A. N. Kuzovlev
“V.A. Negovsky Scientific Research Institute of General Reanimatology” of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation
Russian Federation
Artem N. Kuzovlev, Dr. Sci. (Med.), Deputy Director
107031, Moscow
A. D. Onufrievich
“Main Military Clinical Hospital named after N.N. Burdenko” of the Ministry of Defense of the Russian Federation
Russian Federation
Russian Federation
Alexander D. Onufrievich, Head of the Blood Center
105094, Moscow
V. A. Inozemtsev
“V.A. Negovsky Scientific Research Institute of General Reanimatology” of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation
Russian Federation
Vladimir A. Inozemtsev, Researcher, Laboratory of Biophysics of Cells Membranes in Critical States
107031, Moscow
O. E. Gudkova
“V.A. Negovsky Scientific Research Institute of General Reanimatology” of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation
Russian Federation
Olga E. Gudkova, Senior Researcher, Laboratory of Biophysics of Cells Membranes in Critical States
107031, Moscow
E. A. Sherstyukova
“V.A. Negovsky Scientific Research Institute of General Reanimatology” of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation
Russian Federation
Ekaterina A. Sherstyukova, Cand. Sci. (Biol.), Senior Researcher, Laboratory of Biophysics of Cells Membranes in Critical States
107031, Moscow
References
1. World Health Organization. Blood safety and availability. URL: https://www.who.int/news-room/fact-sheets/detail/blood-safety-and-availability.
2. Akselrod B.A., Balashova E.N., Bautin A.E., et al. Clinical guidelines for red blood cell transfusion. Gematologiya i Transfusiologiya. 2018; 63(4): 372–435. DOI: 10.25837/HAT.2019.62.39.006. (In Russian).
3. European Directorate for the Quality of Medicines & HealthCare of the Council of Europe (EDQM). Guide to the preparation, use and quality assurance of blood components. 19th ed. Strasbourg: EDQM Publishers; 2017.
4. D’Alessandro A., Reisz J.A., Culp-Hill R., et al. Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells. Transfusion. 2018; 58(8): 1992–2002. DOI: 10.1111/trf.14620.
5. Cancelas J.A., Dumont L.J., Maes L.A., et al. Additive solution-7 reduces the red blood cell cold storage lesion. Transfusion. 2015; 55(3): 491–8. DOI: 10.1111/trf.12867.
6. Radwanski K., Thill M., Min K. Red cell storage in E-Sol 5 and Adsol additive solutions: Paired comparison using mixed and non-mixed study designs. Vox Sang. 2014; 106(4): 322–9. DOI: 10.1111/vox.12108.
7. Lagerberg J.W., Korsten H., Van Der Meer P.F., et al. Prevention of red cell storage lesion: A comparison of five different additive solutions. Blood Transfus. 2017; 15(5): 456–62. DOI: 10.2450/2017.0371-16.
8. Shah A., Brunskill S.J., Desborough M.J., et al. Transfusion of red blood cells stored for shorter versus longer duration for all conditions. Cochrane Database Syst Rev. 2018; 12(12): CD010801. DOI: 10.1002/14651858.CD010801.pub3.
9. Bennett-Guerrero E., Rizwan S., Rozensky R., et al. Randomized controlled trial of 7, 28, vs 42 day stored red blood cell transfusion on oxygen delivery (VO(2) max) and exercise duration. Transfusion. 2021; 61(3): 699–707. DOI: 10.1111/trf.16237.
10. Protopopova E.B., Burkitbaev Z.K., Kuzmin N.S., et al. Donor red blood cells storage period does not affect the effectiveness of their transfusion. Vestnik Ntsionalnogo mediko-chirurgicheskogo Centra im N.I. Pirogova. 2015; 10(3): 118–20. (In Russian).
11. DeSantis S.M., Brown D.W., Jones A.R., et al. Characterizing red blood cell age exposure in massive transfusion therapy: the scalar age of blood index (SBI). Transfusion. 2019; 59(8): 2699–708. DOI: 10.1111/trf.15334.
12. Zallen G., Offner P.J., Moore E.E., et al. Age of transfused blood is an independent risk factor for postinjury multiple organ failure. Am J Surg. 1999; 178(6): 570–2. DOI: 10.1016/s0002-9610(99)00239-1.
13. Sparrow R.L. Red blood cell storage duration and trauma. Transfus Med Rev. 2015; 29(2): 120–6. DOI: 10.1016/j.tmrv.2014.09.007.
14. Bishnoi A.K., Garg P., Patel K., et al. Effect of red blood cell storage duration on outcome after paediatric cardiac surgery: A prospective observational study. Heart Lung Circ. 2019; 28(5): 784–91. DOI: 10.1016/j.hlc.2018.03.012.
15. Sanders J., Patel S., Cooper J., et al. Red blood cell storage is associated with length of stay and renal complications after cardiac surgery. Transfusion. 2011; 51(11): 2286–94. DOI: 10.1111/j.1537-2995.2011.03170.x.
16. Steiner M.E., Ness P.M., Assmann S.F., et al. Effects of red-cell storage duration on patients undergoing cardiac surgery. N Engl J Med. 2015; 372(15): 1419–29. DOI: 10.1056/NEJMoa1414219.
17. Kozlova E., Chernysh A., Moroz V., et al. Morphology, membrane nanostructure and stiffness for quality assessment of packed red blood cells. Sci Rep. 2017; 7(1): 7846. DOI: 10.1038/s41598-017-08255-9.
18. Gusev G.P., Govekar R., Gadewal N., Agalakova N.I. Understanding quasi-apoptosis of the most numerous enucleated components of blood needs detailed molecular autopsy. Ageing Res Rev. 2017; 35: 46–62. DOI: 10.1016/j.arr.2017.01.002.
19. Deryugina A.V., Boyarinov G.A., Simutis I.S., et al. Morphological and metabolic parameters of red blood cells after their treatment with ozone. Obschaya Reanimatologiya. 2018; 14(1): 40–9. DOI: 10.15360/1813-9779-2018-1-40-49. (In Russian).
20. Sergunova V., Leesment S., Kozlov A., et al. Investigation of red blood cells by atomic force microscopy. Sensors (Basel). 2022; 22(5): 2055. DOI: 10.3390/s22052055.
21. Kozlova E., Chernysh A., Manchenko E., et al. Nonlinear biomechanical characteristics of deep deformation of native RBC membranes in normal state and under modifier action. Scanning. 2018; 2018: 1810585. DOI: 10.1155/2018/1810585.
22. Manchenko E.A., Kozlova E.K., Sergunova V.A., et al. Homogeneous deformation of native erythrocytes during long-term storage. Obschaya Reanimatologiya. 2019; 15(5): 4–10. DOI: 10.15360/1813-9779-2019-5-4-10. (In Russian).
23. Kozlova E.K., Chernysh A.M., Moroz V.V., Kuzovlev A.N. Analysis of nanostructure of red blood cells membranes by space Fourier transform of AFM images. Micron. 2013; 44: 218–27. DOI: 10.1016/j.micron.2012.06.012.
24. Sherstyukova E.A., Inozemtsev V.A., Kozlov A.P., et al. Atomic force microscopy in the assessment of erythrocyte membrane mechanical properties with exposure to various physicochemical agents. Almanac of Clinical Medicine. 2021; 49(6): 427–34. DOI: 10.18786/2072-0505-2021-49-059. (In Russian).
25. Flatt J.F., Bawazir W.M., Bruce L.J. The involvement of cation leaks in the storage lesion of red blood cells. Front Physiol. 2014; 5: 214. DOI: 10.3389/fphys.2014.00214.
26. Yoshida T., Prudent M., D’alessandro A. Red blood cell storage lesion: Causes and potential clinical consequences. Blood Transfus. 2019; 17(1): 27–52. DOI: 10.2450/2019.0217-18.
27. Decree of the Government of the Russian Federation from June 22, 2019 N 797 “On approval of the Rules of procurement, storage, transportation and clinical use of donor blood and its components and on the invalidation of some acts of the Government of the Russian Federation”. URL: https://docs.cntd.ru/document/560504285. (In Russian).
28. Lamzin I.M., Khayrullin R.M. The study of changes of biophysical properties of red blood cells in storage in erythrocyte-containing solutions using atomic force microscopy. Saratov Journal of Medical Scientific Research. 2014; 10(1): 44–8. (In Russian).
29. Kozlova E., Chernysh A., Moroz V., et al. Two-step process of cytoskeletal structural damage during long-term storage of packed red blood cells. Blood Transfus. 2021; 19(2): 124–34. DOI: 10.2450/2020.0220-20.
30. Delobel J., Prudent M., Rubin O., et al. Subcellular fractionation of stored red blood cells reveals a compartment-based protein carbonylation evolution. J Proteomics. 2012; 76(Spec No): 181–93. DOI: 10.1016/j.jprot.2012.05.004.
31. Sherstyukova E., Chernysh A., Moroz V., et al. The relationship of membrane stiffness, cytoskeleton structure and storage time of pRBCs. Vox Sang. 2021; 116(4): 405–15. DOI: 10.1111/vox.13017.
Review
For citations:
Sergunova V.A., Kuzovlev A.N., Onufrievich A.D., Inozemtsev V.A., Gudkova O.E., Sherstyukova E.A. Conformational disorders of RBC membranes during long-term storage. Russian journal of hematology and transfusiology. 2022;67(2):181-192. (In Russ.) https://doi.org/10.35754/0234-5730-2022-67-2-181-192
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