Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS-III-Omics
Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS-III-Omics
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DOI：
10.1111/trf.14979
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发表时间：
2019-01-01
期刊：
影响因子：
2.9
通讯作者：
Cristman, A. M.
中科院分区：
文献类型：
--
作者：
D'Alessandro, Angelo;Culp-Hill, Rachel;Cristman, A. M.
背景技术背景：生物和技术变异性已越来越被认为是影响红细胞（RBC）可储存性和潜在输血结果的关键因素。在此，我们进行了代谢组学分析，以研究储存时间以外的因素对多中心研究中储存RBC代谢表型的影响。在REDS-III框架内（流行病学和供体评价研究-III）RBC组学研究，13，从美国的四个血液中心招募了403名供体，并在储存42天后测试了他们的RBC溶血倾向。极端溶血剂被召回，并捐赠了第二个单位的血液。单位被存储为10，23，和42天前，从599个选定的样品采集代谢组学analysis.RESULTS：代谢组学数据的无监督分析显示了强烈的影响（14.2%的方差）的存储时间对红细胞代谢表型。血液中心采集和处理单位解释了总方差的另外12.2%，差异主要归因于不同中心使用的储存添加剂（添加剂溶液1与添加剂溶液3）。储存在无甘露醇/柠檬酸盐加载AS-3中的样品的特征在于高能量化合物水平升高、糖酵解改善和谷胱甘肽稳态。在中心使用添加剂溶液1处理的样品中观察到蛋氨酸代谢增加和转硫途径激活。结论：血液处理影响储存RBC的代谢异质性，这是迄今为止输血医学中最大的多中心代谢组学研究。需要进行研究以了解这些受处理/储存策略影响的代谢差异是否会影响临床输血的有效性。
BACKGROUND: Biological and technical variability has been increasingly appreciated as a key factor impacting red blood cell (RBC) storability and, potentially, transfusion outcomes. Here, we performed metabolomics analyses to investigate the impact of factors other than storage duration on the metabolic phenotypes of stored RBC in a multicenter study.STUDY DESIGN AND METHODS: Within the framework of the REDS-III (Recipient Epidemiology and Donor Evaluation Study-III) RBC-Omics study, 13,403 donors were enrolled from four blood centers across the United States and tested for the propensity of their RBCs to hemolyze after 42 days of storage. Extreme hemolyzers were recalled and donated a second unit of blood. Units were stored for 10, 23, and 42 days prior to sample acquisition for metabolomics analyses.RESULTS: Unsupervised analyses of metabolomics data from 599 selected samples revealed a strong impact (14.2% of variance) of storage duration on metabolic phenotypes of RBCs. The blood center collecting and processing the units explained an additional 12.2% of the total variance, a difference primarily attributable to the storage additive (additive solution 1 vs. additive solution 3) used in the different hubs. Samples stored in mannitol-free/citrate-loaded AS-3 were characterized by elevated levels of high-energy compounds, improved glycolysis, and glutathione homeostasis. Increased methionine metabolism and activation of the transsulfuration pathway was noted in samples processed in the center using additive solution 1.CONCLUSION: Blood processing impacts the metabolic heterogeneity of stored RBCs from the largest multicenter metabolomics study in transfusion medicine to date. Studies are needed to understand if these metabolic differences influenced by processing/storage strategies impact the effectiveness of transfusions clinically.