Bordbar Aarash, Johansson Pär I, Paglia Giuseppe, Harrison Scott J, Wichuk Kristine, Magnusdottir Manuela, Valgeirsdottir Sóley, Gybel-Brask Mikkel, Ostrowski Sisse R, Palsson Sirus, Rolfsson Ottar, Sigurjónsson Olafur E, Hansen Morten B, Gudmundsson Sveinn, Palsson Bernhard O
Sinopia Biosciences, San Diego, California.
Section for Transfusion Medicine, Capital Region Blood Bank, Rigshopitalet, University of Copenhagen, Copenhagen, Denmark.
Transfusion. 2016 Apr;56(4):852-62. doi: 10.1111/trf.13460. Epub 2016 Jan 8.
There has been interest in determining whether older red blood cell (RBC) units have negative clinical effects. Numerous observational studies have shown that older RBC units are an independent factor for patient mortality. However, recently published randomized clinical trials have shown no difference of clinical outcome for patients receiving old or fresh RBCs. An overlooked but essential issue in assessing RBC unit quality and ultimately designing the necessary clinical trials is a metric for what constitutes an old or fresh RBC unit.
Twenty RBC units were profiled using quantitative metabolomics over 42 days of storage in SAGM with 3- to 4-day time intervals. Metabolic pathway usage during storage was assessed using systems biology methods. The detected time intervals of the metabolic states were compared to clinical outcomes.
Using multivariate statistics, we identified a nonlinear decay process exhibiting three distinct metabolic states (Days 0-10, 10-17, and 17-42). Hematologic variables traditionally measured in the transfusion setting (e.g., pH, hemolysis, RBC indices) did not distinguish these three states. Systemic changes in pathway usage occurred between the three states, with key pathways changing in both magnitude and direction. Finally, an association was found between the time periods of the metabolic states with the clinical outcomes of more than 280,000 patients in the country of Denmark transfused over the past 15 years and endothelial damage markers in healthy volunteers undergoing autologous transfusions.
The state of RBC metabolism may be a better indicator of cellular quality than traditional hematologic variables.
确定较陈旧的红细胞（RBC）单位是否具有负面临床影响一直受到关注。众多观察性研究表明，较陈旧的RBC单位是患者死亡率的独立因素。然而，最近发表的随机临床试验表明，接受陈旧或新鲜RBC的患者临床结局并无差异。在评估RBC单位质量以及最终设计必要的临床试验时，一个被忽视但至关重要的问题是如何界定陈旧或新鲜RBC单位的标准。
20个RBC单位在添加腺嘌呤、葡萄糖、甘露醇的保存液（SAGM）中储存42天，每隔3至4天进行一次定量代谢组学分析。使用系统生物学方法评估储存期间的代谢途径使用情况。将检测到的代谢状态时间间隔与临床结局进行比较。
使用多变量统计分析，我们确定了一个非线性衰减过程，呈现出三种不同的代谢状态（第0 - 10天、10 - 17天和17 - 42天）。传统上在输血环境中测量的血液学变量（如pH值、溶血、RBC指数）无法区分这三种状态。三种状态之间代谢途径使用发生了系统性变化，关键途径在幅度和方向上都发生了改变。最后，在过去15年丹麦超过280,000例接受输血患者的代谢状态时间段与接受自体输血的健康志愿者的内皮损伤标志物之间发现了关联。
RBC代谢状态可能比传统血液学变量更能反映细胞质量。
