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...
Main Authors: | , , , , , , , , , , , , , , , , , , |
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Format: | Journal article |
Language: | English |
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Elsevier
2024
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_version_ | 1817932559444606976 |
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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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first_indexed | 2024-12-09T03:39:50Z |
format | Journal article |
id | oxford-uuid:cccc624f-7dd9-4359-a75e-2f6be2e60b2d |
institution | University of Oxford |
language | English |
last_indexed | 2024-12-09T03:39:50Z |
publishDate | 2024 |
publisher | Elsevier |
record_format | dspace |
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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