Scientists have developed a way of assessing the ability of red blood cells to deliver oxygen by measuring their shape. This test could improve specialist transplant and transfusion practice as well as blood banking. The research is now published open access in eBioMedicine – part of the Lancet Discovery Science.
FlowScore (1) - a formula developed at Oxford University in collaboration with NHS Blood and Transplant - predicts how quickly red blood cells release their oxygen. This process is important for oxygenating the body’s tissues, including organs and muscles, particularly in people receiving large transfusions.
Healthy fresh red blood cells have a distinctive biconcave – or dumbbell – shape for efficient oxygen release. During refrigerated storage, red cells become energetically stressed and more spherical, which slows oxygen release. Using transplant kidneys, researchers at Oxford showed that perfusion with blood units that had undergone storage-related kinetic rundown was associated with poorer oxygen delivery, and that this could be restored by biochemically rejuvenating - or refreshing - the blood.
Factors affecting oxygen release from red cells were described at Oxford’s Department of Physiology, Anatomy, and Genetics but the testing method was too laborious for routine use in blood agencies working to improve the monitoring of blood stored for transfusion. To adapt the research findings to blood banking, NHS Blood and Transplant's Component Development Laboratory joined the project, providing blood samples stored according to NHS protocols and measurements from haematology analysers.
During routine blood counts, haematology analysers use flow cytometry - a method that passes cells through a laser beam to study their characteristics. When light hits a cell, the pattern of scattering reveals information about their size and shape. It was found that this information accurately predicts oxygen release from red blood cells, and the predictive formula was called FlowScore (2)(3). The innovation makes measurements of red cell oxygen transport simpler, faster, and more accessible for laboratories worldwide.
Blood banks can now use FlowScore as a quality-control measure during processing and storage. For example, FlowScore was able to quantify the beneficial effects of rejuvenation and detect periods of blood handling outside blood bank-grade conditions. The latter may be critical in monitoring stored blood quality in developing countries with higher ambient temperatures. FlowScore could also provide a way to check the quality of blood for specific vulnerable patient groups, should future research show patient benefit (4).
Professor Pawel Swietach, Professor of Physiology at Oxford University, said: 'We find that FlowScore is a robust surrogate of oxygen-handling by red cells and provides new and important information on oxygen transport by the blood. Aside from its applications in transfusion medicine and blood banking, FlowScore can help identify new genetic, environmental and lifestyle factors that influence oxygen delivery to tissues.'
Dr Peter Smethurst, from the NHSBT Blood and Transplant Component Development Laboratory, said: 'FlowScore could become quite fundamental to the way blood is tested to ensure its quality. It is a technical breakthrough that should improve the monitoring of stored blood and drive improvements that will most benefit vulnerable recipients of red cell transfusions.'
Dr Rebecca Cardigan, Head of the NHSBT Blood and Transplant Component Development Laboratory, said: 'FlowScore is an accessible marker of cellular performance to complement other quality metrics. It has been very exciting to conduct this cross-disciplinary and multi-agency collaboration, translating the excellent basic research in Oxford to provide a basis for better assessment of stored blood and transfusion practice across the world.'
- The study is published in eBioMedicine https://doi.org/10.1016/j.ebiom.2024.105498
Read the press release from NHSBT.
Press Release Notes
- The ability of red blood cells to oxygenate tissues depends on how much oxygen they can store, and how quickly this gaseous cargo can be released at systemic capillaries. The former is measured routinely from haemoglobin assays, and their results have defined anaemic thresholds and informed medical guidelines. However, the latter is a kinetic parameter that is technically challenging to measure because it requires resource-intensive methods, such as Oxford’s single-cell oxygen saturation imaging approach. Without a widely-accessible and cost-effective surrogate, appraisal of oxygen-unloading remains aspirational. The study introduces and validates FlowScore: an algorithm for estimating the rate of oxygen-unloading from RBCs using geometry-sensitive light scattering routinely recorded on haematology analysers.
- FlowScore is measured using the reticulocyte channel of standard haematology analysers; FlowScore estimates oxygen-unloading rates from red cell shape interrogated from laser light scattering, providing crucial quality information with minimal additional cost. Since the shape of red cells influences the distance oxygen must travel to exit the cell, FlowScore can be calibrated to give a direct indication of oxygen-unloading rate.
- The results were benchmarked against data from Australian Red Cross Lifeblood, Canadian Blood Services, NHS Blood and Transplant, and Banc de Sang i Teixits (Spain). Sysmex, the haematology analyser manufacturer, supported the benchmarking exercise by providing the same batches of QC material to each of the partners at exactly the same time, through their worldwide distribution network .
- More than a million red cell units are transfused each year in the UK. After blood is donated, red cells are separated and suspended in additive solution under refrigerated conditions intended to preserve quality for up to five weeks.
Organisational Notes
- NHS Blood and Transplant is a joint England and Wales Special Health Authority. We provide the blood donation service for England and the organ donation service for the UK. We also provide donated tissues, stem cells and cord blood. We are an essential part of the NHS, saving and improving lives through public donation.
- The Department of Physiology, Anatomy and Genetics is a major discovery science research unit within the Division of Medical Sciences at the University of Oxford. The department is a bridge to translational medicine, and an interface between the physical and life sciences. The Department is home to a large number of internationally-renowned scientists addressing major questions in medical science. The departments ranked #1 for Anatomy and Physiology in the QS World University Rankings by subject 2017, 2018, 2020, 2021, 2022, 2023, 2024.