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

用于诊断和管理贫血以及监测储存血液质量的新型溶血生物标志物和单细胞气体交换成像

• 批准号: EP/X021548/1
• 负责人: Pawel Swietach
• 金额: $ 16.47万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX021548%2F1
• 关键词: Novel; haemolytic; biomarkers; single; cell

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.

为了生存，组织需要由血液提供足够的氧气。这项任务有两个方面：（i）血液的O2携带能力必须足够高，以及（ii）血液中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，人体中每五个真核细胞就有一个RBC。每个红细胞在大约30秒内在身体内移动，包括通过气体交换的毛细血管的短暂停留。尽管有这些适应措施，但贫血仍是影响全球健康的最常见疾病。由于贫血包括一系列条件，准确的诊断是正确的管理至关重要。改善贫血症气体输送的一种常见干预措施是输注储存的血液制品。尽管研究激增，但定义贫血的临床阈值是基于四十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的气体处理如何在某些血液学条件下和储存的血液单位中变得非常缓慢。我们的研究结果为“动力性贫血”提供了一个案例，这是一种新的疾病，目前的血液分析仪无法检测到，但在贫血定义和指南中值得考虑。该提案解释了我们将如何通过研究血液病患者来为动力性贫血提供临床案例。我们还建议将我们的方法应用于筛选储存的血液中的气体交换动力学。这样的质量控制可以改善血库的资源分配，并使储存制度对输血效果的影响的可靠的临床试验成为可能。最近，我们描述了如何尿排泄CAI是一个方便的生物标志物溶血的新生儿。我们建议开发CAI检测设备，并测试其诊断溶血的能力。我们的目标是将这种资源有效的设备部署到经济贫困的地区，那里溶血更普遍。

项目成果

Metabolic reprogramming under hypoxic storage preserves faster oxygen unloading from stored red blood cells.

• DOI: 10.1182/bloodadvances.2022007774
• 发表时间: 2022-09-27
• 期刊: BLOOD ADVANCES
• 影响因子: 7.5
• 作者: Rabcuka, Julija;Blonski, Slawomir;Meli, Athinoula;Sowemimo-Coker, Samuel;Zaremba, Damian;Stephenson, Daniel;Dzieciatkowska, Monika;Nerguizian, David;Cardigan, Rebecca;Korczyk, Piotr M.;Smethurst, Peter A.;D'Alessandro, Angelo;Swietach, Pawel
• 通讯作者: Swietach, Pawel

Impaired O2 unloading from stored blood results in diffusion-limited O2 release at tissues: evidence from human kidneys.

储存血液中的 O2 卸载受损会导致组织中 O2 释放受到扩散限制：来自人类肾脏的证据。

• DOI: 10.1182/blood.2023022385
• 发表时间: 2024
• 期刊: Blood
• 影响因子: 20.3
• 作者: Dumbill R