2026-04-13T01:30:41Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/129532025-10-24T08:47:43Zcom_2072_378071com_2072_378040col_2072_378097
RECERCAT
author
Rabcuka, Julija
author
Smethurst, Peter
author
Dammert, Katharina
author
Saker, Jarob
author
Aran , Gemma
author
Walsh, Geraldine M.
author
Codinach, Margarita
2025-10-24T08:47:43Z
2025-10-24T08:47:43Z
2025-04-14T08:52:07Z2025-04-14T08:52:07Z20242025-01
http://hdl.handle.net/11351/12953
Erythrocytes; Oxygen transport; Storage lesionEritrocitos; Transporte de oxígeno; Lesión por almacenamientoEritròcits; Transport d'oxigen; Lesió d'emmagatzematgeBackground
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 (τ), measured using single-cell oxygen saturation imaging, with flow-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 τ 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 τ 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.Research was selected by the European Research Council and funded by UKRI (ERC and MSCA Other Guarantee Calls), EP/X021548/1 (to P.S.), the John Fell Fund grant #0010677 (to P.S.), NHS Blood and Transplant grant #146TRAN24 (to R.C.), and First Team grant (POIR.04.04.00-00-3FEF/17-00) of the Foundation for Polish Science co-financed by the EU under the Smart Growth Operational Program (to P.M.K.). JR and PAS received consumables from Sysmex Europe. Participants in the COMPARE study were recruited with the active collaboration of NHS Blood and Transplant (NHSBT) England (www.nhsbt.nhs.uk). Funding was provided by NHSBT and the NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (NIHR BTRU-2014-10024). Australian governments fund Australian Red Cross Lifeblood to provide blood, blood products and services to the Australian community. Canadian Blood Services are funded by the federal government (Health Canada) and the provincial and territorial ministries of health. The views herein do not necessarily reflect the views of the federal, provincial, or territorial governments of Canada. DNA extraction and genotyping were co-funded by the NIHR BTRU and the NIHR BioResource (http://bioresource.nihr.ac.uk). The academic coordinating centre for COMPARE is supported by core funding from the: NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (NIHR BTRU-2014-10024), NIHR BTRU in Donor Health and Behaviour (NIHR203337), UK Medical Research Council (MR/L003120/1), British Heart Foundation (SP/09/002; RG/13/13/30194; RG/18/13/33946) and NIHR Cambridge BRC (BRC-1215-20014; NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The academic coordinating centre would like to thank blood donor centre staff and blood donors for participating in the COMPARE study. A complete list of the investigators and contributors to the COMPARE study is provided earlier.30 The LifeLines initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG), Groningen University and the Provinces in the North of the Netherlands (Drenthe, Friesland, Groningen).
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
Sang - Recollida i conservació
Eritròcits
Citometria de fluxe
Oxigen
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Separation::Flow Cytometry
ANATOMY::Cells::Blood Cells::Erythrocytes
CHEMICALS AND DRUGS::Inorganic Chemicals::Elements::Chalcogens::Oxygen
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Preservation, Biological::Tissue Preservation::Blood Preservation
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::técnicas citológicas::separación celular::citometría de flujo
ANATOMÍA::células::células sanguíneas::eritrocitos
COMPUESTOS QUÍMICOS Y DROGAS::compuestos inorgánicos::elementos::calcógenos::oxígeno
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::conservación biológica::conservación de tejidos::conservación de la sangre
Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion