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Ferrata Storti Foundation
Haematologica 2022 Volume 107(1):112-125
Beta thalassemia minor is a beneficial determinant of red blood cell storage lesion
Vassilis L. Tzounakas,1* Alkmini T. Anastasiadi,1* Davide Stefanoni,2 Francesca Cendali,2 Lorenzo Bertolone,2 Fabia Gamboni,2 Monika Dzieciatkowska,2 Pantelis Rousakis,3 Athina Vergaki,4 Vassilis Soulakis,4 Ourania E. Tsitsilonis,3 Konstantinos Stamoulis,5 Issidora S. Papassideri,1 Anastasios G. Kriebardis,6 Angelo D’Alessandro2 and Marianna H. Antonelou1
1Department of Biology, Section of Cell Biology and Biophysics, School of Science, National and Kapodistrian University of Athens (NKUA), Athens, Greece; 2Department of Biochemistry and Molecular Genetics, University of Colorado, School of Medicine– Anschutz Medical Campus, Aurora, CO, USA; 3Department of Biology, Section of Animal and Human Physiology, School of Science (NKUA), Athens, Greece; 4Regional Blood Transfusion Center, “Agios Panteleimon” General Hospital of Nikea, Piraeus, Greece; 5Hellenic National Blood Transfusion Center, Acharnes, Athens, Greece and 6Department of Biomedical Science, School of Health & Caring Science, University of West Attica (UniWA), Egaleo, Greece.
*VLT and ATA contributed equally as co-first authors.
ABSTRACT
Blood donor genetics and lifestyle affect the quality of red blood cell (RBC) storage. Heterozygotes for beta thalassemia (bThal+) constitute a non-negligible proportion of blood donors in the Mediterranean and other geographical areas. The unique hematological profile of bThal+ could affect the capacity of enduring storage stress, however, the storability of bThal+ RBC is largely unknown. In this study, RBC from 18 bThal+ donors were stored in the cold and profiled for primary (hemolysis) and secondary (phosphatidylserine exposure, potassium leakage, oxidative stress) quality measures, and metabolomics, versus sex- and age-matched controls. The bThal+ units exhibited better levels of storage hemolysis and susceptibility to lysis following osmotic, oxidative and mechanical insults. Moreover, bThal+ RBC had a lower percentage of surface removal signaling, reactive oxy- gen species and oxidative defects to membrane components at late stages of storage. Lower potassium accumulation and higher urate- dependent antioxidant capacity were noted in the bThal+ supernatant. Full metabolomics analyses revealed alterations in purine and arginine pathways at baseline, along with activation of the pentose phosphate pathway and glycolysis upstream to pyruvate kinase in bThal+ RBC. Upon storage, substantial changes were observed in arginine, purine and vitamin B6 metabolism, as well as in the hexosamine pathway. A high degree of glutamate generation in bThal+ RBC was accompanied by low levels of purine oxidation products (IMP, hypoxanthine, allan- toin). The bThal mutations impact the metabolism and the susceptibil- ity to hemolysis of stored RBC, suggesting good post-transfusion recov- ery. However, hemoglobin increment and other clinical outcomes of bThal+ RBC transfusion deserve elucidation by future studies.
Introduction
Inter-donor heterogeneity significantly impacts the two “gold standards” of red blood cell (RBC) storage quality, namely end of storage hemolysis and in vivo 24- hour post-transfusion recovery.1 Donor age, sex, ethnicity2 and lifestyle (smoking, drinking, caffeine consumption3) all impact stored RBC energy and redox metab- olism, and thereby RBC capacity to cope with oxidant and other insults. These factors ultimately affect transfusion efficacy, as gleaned by outcomes like hemo- globin (Hb) increments upon transfusion.4 Genetic factors impacting RBC redox status and antioxidant capacity have been linked to alteration of the metabolic age
Blood Transfusion
Correspondence:
MARIANNA H. ANTONELOU
manton@biol.uoa.gr
ANGELO D’ALESSANDRO
angelo.dalessandro@cuanschutz.edu
Received: October 6, 2020. Accepted: December 4, 2020. Pre-published: March18,2021.
https://doi.org/10.3324/haematol.2020.273946 ©2022 Ferrata Storti Foundation
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