Corpuscular Fragility and Metabolic Aspects of Freshly Drawn Beta-Thalassemia Minor RBCs Impact Their Physiology and Performance Post Transfusion: A Triangular Correlation Analysis In Vitro and In Vivo.

Alkmini T Anastasiadi,Konstantinos Stamoulis,Vasiliki-Zoi Arvaniti,Issidora S Papassideri,Anastasios G Kriebardis,Angelo D’Alessandro,Vassilis L Tzounakas,Efthymios C Paronis,Nikolaos G Kostomitsopoulos,Marianna H Antonelou

doi:10.3390/biomedicines10030530

Abstract

The clarification of donor variation effects upon red blood cell (RBC) storage lesion and transfusion efficacy may open new ways for donor–recipient matching optimization. We hereby propose a “triangular” strategy for studying the links comprising the transfusion chain—donor, blood product, recipient—as exemplified in two cohorts of control and beta-thalassemia minor (βThal+) donors (n = 18 each). It was unraveled that RBC osmotic fragility and caspase-like proteasomal activity can link both donor cohorts to post-storage states. In the case of heterozygotes, the geometry, size and intrinsic low RBC fragility might be lying behind their higher post-storage resistance to lysis and recovery in mice. Moreover, energy-related molecules (e.g., phosphocreatine) and purine metabolism factors (IMP, hypoxanthine) were specifically linked to lower post-storage hemolysis and phosphatidylserine exposure. The latter was also ameliorated by antioxidants, such as urate. Finally, higher proteasomal conservation across the transfusion chain was observed in heterozygotes compared to control donors. The proposed “triangularity model” can be (a) expanded to additional donor/recipient backgrounds, (b) enriched by big data, especially in the post-transfusion state and (c) fuel targeted experiments in order to discover new quality biomarkers and design more personalized transfusion medicine schemes.

Highlights

While originally suggested by the middle of the 1960s [1], the concept of donor variation effects, namely, that blood donors’ characteristics, both genetic and environmental, may affect the storability and post-transfusion efficacy of red blood cells (RBCs) [2,3], has only been established in the last decade
The unique physiology and RBC storability of these distinctive donor groups may be linked to differential post-transfusion phenotypes
To better clarify the proposed analysis method, we applied it to RBCs from average control and beta-thalassemia minor donors pre, during and post-storage, using in vitro and in vivo models of transfusion

Summary

Introduction

While originally suggested by the middle of the 1960s [1], the concept of donor variation effects, namely, that blood donors’ characteristics, both genetic and environmental, may affect the storability and post-transfusion efficacy of red blood cells (RBCs) [2,3], has only been established in the last decade. In terms of transfusion outcome, blood units from female donors have been proposed to be better for same-sex recipients [4,5], Biomedicines 2022, 10, 530. The osmotic fragility of RBCs in transfusion-mimicking conditions is proportional to that of freshly drawn and stored counterparts [14]. Both storage and osmotic types of hemolysis have been negatively associated with the recovery of RBCs from obese subjects [8]. We hereby propose a more “complete” model to study the transfusion chain, by performing paired donor-blood unit-recipient analyses and trying to link—directly or indirectly—freshly drawn blood characteristics with transfusion outcomes. To better clarify the proposed analysis method, we applied it to RBCs from average control and beta-thalassemia minor donors pre-, during and post-storage, using in vitro and in vivo models of transfusion

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