Novel haemolytic biomarkers and single-cell gas exchange imaging for diagnosing and managing anaemias and for monitoring the quality of stored blood

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To survive, tissues require an adequate supply of oxygen delivered by blood. There are two aspects to this task: (i) the blood's O2-carrying capacity must be sufficiently high and (ii) gas exchange to and from blood must be sufficiently fast. To maximise capacity, O2-carrying red blood cells (RBCs) are highly abundant, with every 5th eukaryotic cell in the human body being an RBC. Each RBC travels around the body in ~30 s, including a brief sojourn through capillaries where gases are exchanged. Notwithstanding these adaptations, anaemia is the single most common disorder affecting health globally. Since anaemias encompass a range of conditions, accurate diagnosis is critical for proper management. A common intervention given to improve gas transport in anaemia is transfusion of stored blood products.Despite a surge in research, clinical thresholds for defining anaemias are based on WHO guidelines compiled four decades ago. Recently, our single-cell methods have described how gas handling by RBCs can become critically slow in certain haematological conditions and in blood units under storage. Our findings make a case for 'kinetic anaemia', a novel condition that is not detected with current haematology analysers but merits consideration in anaemic definitions and guidelines. This proposal explains how we will make the clinical case for kinetic anaemia by studying haematological patients. We also propose to apply our methods to screen stored bloods in terms of gas-exchange kinetics. Such quality-control can improve resource allocation in blood banks and enable robust clinical trials of the effect of storage regimes on transfusion efficacy. Recently, we described how urinary excretion of CAI is a convenient biomarker for haemolysis in the newborn. We propose to develop CAI detection devices and test their power to diagnose haemolysis. Our is aim is to deploy such resource-efficient devices to economically-deprived regions where haemolysis is more prevalent.