Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a fl ow-cytometric proxy of the functional quality of blood

被引：0

作者：

Rabcuka, Julija ^{[1
]}

Smethurst, Peter A. ^{[2
]}

Dammert, Katharina ^{[3
]}

Saker, Jarob ^{[3
]}

Aran, Gemma ^{[4
]}

Walsh, Geraldine M. ^{[5
]}

Tan, Joanne C. G. ^{[6
]}

Codinach, Margarita ^{[4
,7
]}

Mctaggart, Ken

Marks, Denese C. ^{[6
,8
]}

Bakker, Stephan J. L. ^{[9
]}

Mcmahon, Amy ^{[10
,11
,12
]}

Di Angelantonio, Emanuele ^{[10
,11
,12
,13
,14
,15
,16
]}

Roberts, David J. ^{[17
,18
]}

Blonski, Slawomir ^{[19
]}

Korczyk, Piotr M. ^{[19
]}

Shirakami, Atsushi ^{[20
]}

Cardigan, Rebecca ^{[21
]}

Swietach, Pawel ^{[1
]}

机构：

[1] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England

[2] NHS Blood & Transplant, Component Dev Lab, Cambridge, England

[3] Sysmex Europe SE, Bornbarch 1, D-22848 Norderstedt, Germany

[4] Banc Sang & Teixits, Cell Lab, Barcelona, Spain

[5] Canadian Blood Serv, Prod & Proc Dev, Vancouver, BC, Canada

[6] Australian Red Cross Lifeblood, Res & Dev, Sydney, Australia

[7] Univ Autonoma Barcelona, Vall dHebron Res Inst, Transfus Med Grp, Barcelona, Spain

[8] Univ Sydney, Sydney Med Sch, Camperdown, NSW, Australia

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands

[10] Univ Cambridge, British Heart Fdn Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England

[11] Univ Cambridge, Victor Phillip Dahdaleh Heart & Lung Res Inst, Cambridge, England

[12] Univ Cambridge, Natl Inst Hlth & Care Res, Blood & Transplant Res Unit Donor Hlth & Behav, Cambridge, England

[13] Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England

[14] Hlth Data Res UK Cambridge, Wellcome Genome Campus, Cambridge, England

[15] Univ Cambridge, Cambridge, England

[16] HDSC Hlth Data Sci Ctr, Human Technopole, Milan, Italy

[17] NHS Blood & Transplant, John Radcliffe Hosp, Oxford, England

[18] Univ Oxford, Radcliffe Dept Med, Oxford, England

[19] Polish Acad Sci, Inst Fundamental Technol Res, Warsaw, Poland

[20] Sysmex Corp, Med & Sci Affairs, Kobe, Japan

[21] Univ Cambridge, Dept Haematol, Cambridge, England

来源：

EBIOMEDICINE | 2025年 / 111卷

基金：

英国医学研究理事会;

关键词：

Haematology; Erythrocytes; Storage lesion; Assay; Oxygen transport; Transfusion; STORAGE LESION; TRANSFUSION; TRANSPORT; METABOLISM; DIFFUSION; IMPROVES; OUTCOMES; ENERGY; AGE;

D O I：

10.1016/j.ebiom.2024.105498

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Metrics evaluating the functional quality of red blood cells (RBCs) must consider their role in oxygen delivery. Whereas oxygen-carrying capacity is routinely reported using haemoglobin assays, the rate of oxygen exchange is not measured, yet also important for tissue oxygenation. Since oxygen-unloading depends on the diffusion pathlength inside RBCs, cell geometry offers a plausible surrogate. Methods We related the time-constant of oxygen-unloading (tau), measured using single-cell oxygen saturation imaging, with fl ow-cytometric variables recorded on a haematology analyser. Experiments compared freshly-drawn RBCs with stored RBCs, wherein metabolic run-down and spherical remodelling hinder oxygen unloading. Findings Multivariable regression related tau to a ratio of side- and forward-scatter, referred to herein as FlowScore. FlowScore was able to distinguish, with sensitivity and specificity >80%, freshly drawn blood from blood that underwent storage-related kinetic attrition in O2-handling. Moreover, FlowScore predicted tau restoration upon biochemical rejuvenation of stored blood. Since RBC geometry and metabolic state are related, variants of FlowScore estimated [ATP] and [2,3-diphosphoglycerate]. The veracity of FlowScore was confirmed by four blood-banking systems (Australia, Canada, England, Spain). Applying FlowScore to data from the COMPARE study revealed a positive association with the time-delay from sample collection to measurement, which was verified experimentally. The LifeLines dataset revealed age, sex, and smoking among factors affecting FlowScore. Interpretation We establish FlowScore as a widely-accessible and cost-effective surrogate of RBC oxygen-unloading kinetics. As a metric of a cellular process that is sensitive to storage and disease, we propose FlowScore as an RBC quality marker for blood-banking and haematology. Funding See Acknowledgements. Copyright (c) 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

引用

页数：18