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Letters to the Editor
ics. Our assay identified major differences between donor units in the progression of O2-handling dysfunction under storage. The extent to which a gene-function cor- relation underpins this variation is testable with our method. The normalization of biochemical and flow- cytometric parameters with rejuvenation explains how O2 handling is also restored to physiological levels. These observations are significant because of renewed interest in optimizing blood storage regimes for patients receiving large transfusions (in whom cumulative effects of storage lesion can be profound), or patients undergoing proce- dures in which sub-optimal tissue oxygenation may result in organ injury.
Several high-quality randomized controlled trials14
have shown that transfusion of blood after prolonged
storage is not associated with higher rates of adverse clin-
ical outcomes than those after transfusion of blood stored
for shorter periods. However, these trials mainly recruit-
ed participants with stable anemia and without an immi-
nent threat to organ perfusion, and did not include
patients requiring massive transfusion or those with
major trauma,14 i.e., cohorts for whom the consequences
of impaired gas exchange kinetics are most relevant. In
the case of transfusion for major hemorrhage, the clinical
imperative is to restore tissue oxygenation immediately.
To achieve this, donated RBC must be capable of
exchanging gases efficiently at the point of transfusion.
This imperative is less relevant in patients with stable
anemia because there is evidence that [2,3-DPG] recovers
upon re-exposure to a physiological milieu, albeit slowly
over up to 3 days.15 A functional assessment of the recov-
ery of O -handling kinetics in vivo is warranted to deter- 2
mine how the efficacy of transfusion depends on the clin- ical context of the recipient.
In the aforementioned trials, randomizations were
based on storage duration rather than high-quality meas-
urements of RBC physiology. We find that time in storage
does not adequately describe the deterioration in O2-han-
dling kinetics, and therefore the use of storage duration
for treatment allocation may have compromised the sta-
tistical power to detect adverse clinical outcomes related
to storage lesion. These considerations may explain the
lack of a statistically significant effect of different storage
regimes in participants with stable anemia. Given that
O -handling kinetics are mechanistically related to the 2
physiological quality of transfused units, we propose that future investigations should consider RBC function, as determined from O2-unloading kinetics or suitable prox- ies.
Killian Donovan,1 Athinoula Meli,2 Francesca Cendali,3 Kyung Chan Park1 Rebecca Cardigan,2,4 Simon Stanworth,5,6,7 Stuart McKechnie,8 Angelo D’Alessandro,3
Peter A. Smethurst2 and Pawel Swietach1
1Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK; 2Component Development Laboratory, NHS Blood and Transplant, Cambridge, UK; 3Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 4Department of Haematology, University of Cambridge, Cambridge, UK; 5Transfusion Medicine, NHS Blood and Transplant, Oxford, UK; 6Department of Haematology, Oxford University Hospitals NHS Foundation Trust,
Oxford, UK; 7Radcliffe Department of Medicine, University of Oxford, and Oxford BRC Haematology Theme, Oxford, UK and 8Adult Intensive Care Unit, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Correspondence:
PAWEL SWIETACH - pawel.swietach@dpag.ox.ac.uk doi:10.3324/haematol.2021.279296
Received: May 26, 2021.
Accepted: September 1, 2021.
Pre-published: September 9, 2021.
Disclosures: no conflicts of interest to disclose.
Contributions: KD, AM, FC, KCP, AD'A, PAS and PS performed research; PS, PAS, AD'A, AM, KD and RC designed and supervised the study; KD, PS, FC and AD'A analyzed the data; PS, KD, AM, SS, SM, AD'A and PAS wrote the manuscript.
Acknowledgments: we thank Drs Jarob Saker and Jean-Pierre Perol (Sysmex, Europe) for discussions on interpreting SSC measurements.
References
1.Bennett-Guerrero E, Veldman TH, Doctor A, et al. Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci U S A. 2007; 104(43):17063-17068.
2. Yoshida T, Prudent M, D'Alessandro A. Red blood cell storage lesion: causes and potential clinical consequences. Blood Transfus. 2019; 17(1):27-52.
3. Tzounakas VL, Georgatzakou HT, Kriebardis AG, et al. Donor vari- ation effect on red blood cell storage lesion: a multivariable, yet con- sistent, story. Transfusion. 2016;56(6):1274-1286.
4. D'Alessandro A, Fu X, Kanias T, et al. Donor sex, age and ethnicity impact stored red blood cell antioxidant metabolism through mech- anisms in part explained by glucose 6-phosphate dehydrogenase lev- els and activity. Haematologica. 2021;106(5):1290-1302.
5. Hess JR. Measures of stored red blood cell quality. Vox Sang. 2014; 107(1):1-9.
6. Roussel C, Dussiot M, Marin M, et al. Spherocytic shift of red blood cells during storage provides a quantitative whole cell-based marker of the storage lesion. Transfusion. 2017;57(4):1007-1018.
7. Richardson SL, Hulikova A, Proven M, et al. Single-cell O2 exchange imaging shows that cytoplasmic diffusion is a dominant barrier to efficient gas transport in red blood cells. Proc Natl Acad Sci U S A. 2020;117(18):10067-10078.
8. Carson JL, Stanworth SJ, Alexander JH, et al. Clinical trials evaluating red blood cell transfusion thresholds: an updated systematic review and with additional focus on patients with cardiovascular disease. Am Heart J. 2018;200:96-101.
9. Trivella M, Stanworth SJ, Brunskill S, Dutton P, Altman DG. Can we be certain that storage duration of transfused red blood cells does not affect patient outcomes? BMJ. 2019;365:l2320.
10. Chng KZ, Ng YC, Namgung B, et al. Assessment of transient changes in oxygen diffusion of single red blood cells using a microfluidic ana- lytical platform. Commun Biol. 2021;4(1):271.
11. Smethurst PA, Jolley J, Braund R, et al. Rejuvenation of RBCs: valida- tion of a manufacturing method suitable for clinical use. Transfusion. 2019;59(9):2952-2963.
12. Stefanoni D, Shin HKH, Baek JH, et al. Red blood cell metabolism in Rhesus macaques and humans: comparative biology of blood stor- age. Haematologica. 2020;105(8):2174-2186.
13. Paglia G, D'Alessandro A, Rolfsson O, et al. Biomarkers defining the metabolic age of red blood cells during cold storage. Blood. 2016; 128(13):e43-50.
14. McQuilten ZK, French CJ, Nichol A, Higgins A, Cooper DJ. Effect of age of red cells for transfusion on patient outcomes: a systematic review and meta-analysis. Transfus Med Rev. 2018;32(2):77-88.
15. Scott AV, Nagababu E, Johnson DJ, et al. 2,3-Diphosphoglycerate concentrations in autologous salvaged versus stored red blood cells and in srgical patients after transfusion. Anesth Analg. 2016;122(3): 616-623.
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