| 1. | Rabcuka J.♦, Smethurst P. A.♦, Dammert K.♦, Saker J.♦, Aran G.♦, Walsh G. M.♦, Tan J. C. G.♦, Codinach M.♦, McTaggart K.♦, Marks D. C.♦, Bakker S. J. L.♦, McMahon A.♦, Di Angelantonio E.♦, Roberts D. J.♦, Błoński S., Korczyk P.M., 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, eBioMedicine, ISSN: 2352-3964, DOI: 10.1016/j.ebiom.2024.105498, Vol.111, pp.105498-105498, 2025 Streszczenie: 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 (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. Słowa kluczowe: Haematology,Erythrocytes,Storage lesion,Assay,Oxygen transport,Transfusion Afiliacje autorów: | Rabcuka J. | - | other affiliation | | Smethurst P. A. | - | other affiliation | | Dammert K. | - | other affiliation | | Saker J. | - | other affiliation | | Aran G. | - | other affiliation | | Walsh G. M. | - | other affiliation | | Tan J. C. G. | - | other affiliation | | Codinach M. | - | other affiliation | | McTaggart K. | - | other affiliation | | Marks D. C. | - | other affiliation | | Bakker S. J. L. | - | other affiliation | | McMahon A. | - | other affiliation | | Di Angelantonio E. | - | other affiliation | | Roberts D. J. | - | other affiliation | | Błoński S. | - | IPPT PAN | | Korczyk P.M. | - | IPPT PAN | | Shirakami A. | - | other affiliation | | Cardigan R. | - | other affiliation | | Swietach P. | - | other affiliation |
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