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

为了生存，组织需要通过血液输送足够的氧气。这项任务包括两个方面：(I)血液携带氧气的能力必须足够高；(Ii)进出血液的气体交换必须足够快。为了最大限度地提高容量，携带氧气的红细胞(RBC)非常丰富，人体内每5个真核细胞就有一个RBC。每个RBC在~30岁的S体内周游，包括在交换气体的毛细血管中短暂停留。尽管有这些适应，贫血症仍是影响全球健康的最常见疾病。由于贫血包括一系列情况，准确的诊断对于适当的治疗至关重要。一种常见的干预措施是输注储存的血液产品，以改善贫血的气体运输。尽管研究激增，但定义贫血的临床阈值是基于40年前编制的世卫组织指南。最近，我们的单细胞方法描述了红细胞如何在某些血液学条件下和储存中的血液单位中处理气体变得极其缓慢。我们的发现为“运动性贫血”提供了一个案例，这是一种新的疾病，目前的血液学分析仪还没有检测到这种疾病，但在贫血的定义和指南中值得考虑。这项建议解释了我们将如何通过研究血液病患者来实现运动性贫血的临床病例。我们还建议将我们的方法应用于从气体交换动力学的角度筛选储存的血液。这种质量控制可以改善血库的资源分配，并能够对储存制度对输血效果的影响进行强有力的临床试验。最近，我们描述了尿液中CaI的排泄如何成为新生儿溶血的一种方便的生物标志物。我们建议开发计算机辅助诊断溶血检测装置，并测试其诊断溶血的能力。我们的目标是将这种资源高效的设备部署到溶血更普遍的经济贫困地区。

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.