| Summary: | <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.
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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.
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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.
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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.
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Funding: </p></strong>See acknowledgements.
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