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

<p><strong>Background: </p></strong>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, y...

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Main Authors: Rabcuka, J, Smethurst, P, Dammert, K, Saker, J, Aran, G, Walsh, G, Tan, J, Codinach, M, McTaggart, K, Marks, D, Bakker, S, McMahon, A, Di Angelantonio, E, Roberts, D, Blonski, S, Korczyk, P, Shirakami, A, Cardigan, R, Swietach, P
Format: Journal article
Language:English
Published: Elsevier 2024
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author Rabcuka, J
Smethurst, P
Dammert, K
Saker, J
Aran, G
Walsh, G
Tan, J
Codinach, M
McTaggart, K
Marks, D
Bakker, S
McMahon, A
Di Angelantonio, E
Roberts, D
Blonski, S
Korczyk, P
Shirakami, A
Cardigan, R
Swietach, P
author_facet Rabcuka, J
Smethurst, P
Dammert, K
Saker, J
Aran, G
Walsh, G
Tan, J
Codinach, M
McTaggart, K
Marks, D
Bakker, S
McMahon, A
Di Angelantonio, E
Roberts, D
Blonski, S
Korczyk, P
Shirakami, A
Cardigan, R
Swietach, P
author_sort Rabcuka, J
collection OXFORD
description <p><strong>Background: </p></strong>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. <p><strong> Methods: </p></strong>We related the time-constant of oxygen-unloading ($\tau$), 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. <p><strong> Findings: </p></strong>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. <p><strong> Interpretation: </p></strong>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. <p><strong> Funding: </p></strong>See acknowledgements.
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spelling oxford-uuid:cccc624f-7dd9-4359-a75e-2f6be2e60b2d2024-12-06T10:57:35ZAssessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of bloodJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cccc624f-7dd9-4359-a75e-2f6be2e60b2dEnglishSymplectic ElementsElsevier2024Rabcuka, JSmethurst, PDammert, KSaker, JAran, GWalsh, GTan, JCodinach, MMcTaggart, KMarks, DBakker, SMcMahon, ADi Angelantonio, ERoberts, DBlonski, SKorczyk, PShirakami, ACardigan, RSwietach, P<p><strong>Background: </p></strong>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. <p><strong> Methods: </p></strong>We related the time-constant of oxygen-unloading ($\tau$), 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. <p><strong> Findings: </p></strong>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. <p><strong> Interpretation: </p></strong>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. <p><strong> Funding: </p></strong>See acknowledgements.
spellingShingle Rabcuka, J
Smethurst, P
Dammert, K
Saker, J
Aran, G
Walsh, G
Tan, J
Codinach, M
McTaggart, K
Marks, D
Bakker, S
McMahon, A
Di Angelantonio, E
Roberts, D
Blonski, S
Korczyk, P
Shirakami, A
Cardigan, R
Swietach, P
Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood
title Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood
title_full Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood
title_fullStr Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood
title_full_unstemmed Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood
title_short Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood
title_sort assessing the kinetics of oxygen unloading from red cells using flowscore a flow cytometric proxy of the functional quality of blood
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