Metabolic impact of red blood cell exchange with rejuvenated red blood cells in sickle cell patients
Metabolic impact of red blood cell exchange with rejuvenated red blood cells in sickle cell patients
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DOI：
10.1111/trf.15467
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发表时间：
2019-08-05
期刊：
影响因子：
2.9
通讯作者：
D'Alessandro, Angelo
中科院分区：
文献类型：
--
作者：
Gehrke, Sarah;Shah, Nirmish;D'Alessandro, Angelo
红细胞交换（RCE）输血是治疗镰状细胞性贫血（SCA）的主要手段，并且允许暂时恢复关于红细胞携氧能力和系统代谢的生理参数。最近，我们注意到1）RCE显著影响SCA中受体的代谢; 2）新鲜和储存结束的红细胞（RBC）单位不同地影响健康自体受体的代谢系统; 3）磷酸盐/肌苷/丙酮酸盐/腺嘌呤（PIPA）溶液逆转储存RBC的代谢年龄。因此，我们假设使用PIPA处理的RBC单位的RCE可以进一步增加SCA患者中RCE的代谢益处。研究设计和方法：在进行代谢组学分析之前，在RCE之前和之后收集SCA患者的循环血浆和红细胞，使用常规或PIPA处理的RBC单位。结果与先前的工作一致，RCE显着降低循环水平的标志物系统性低氧血症（乳酸，琥珀酸）和降低血浆水平的酰基-肉毒碱和氨基酸。然而，PIPA处理的交换上级未处理的RCE，具有更高的能量状态和增加的激活戊糖磷酸途径和谷氨酰胺代谢的能力。此外，来自接受PIPA处理的RBC单位的RBC和血浆导致输血后增塑剂水平显著降低，但以较高的氧化嘌呤（次黄嘌呤、黄嘌呤和抗氧化剂尿酸盐）循环水平为代价。结论输注PIPA处理的红细胞进一步增加了SCA患者RCE的代谢益处，显著降低了输注后增塑剂的水平。
BACKGROUND Red blood cell exchange (RCE) transfusions are a mainstay in the treatment of sickle cell anemia (SCA), and allow a temporary restoration of physiological parameters with respect to erythrocyte oxygen carrying capacity and systems metabolism. Recently, we noted that 1) RCE significantly impacts recipients' metabolism in SCA; 2) fresh and end-of-storage red blood cell (RBC) units differently impact systems of metabolism in healthy autologous recipients; and 3) phosphate/inosine/pyruvate/adenine (PIPA) solution reverses the metabolic age of stored RBCs. Therefore, we hypothesized that RCE with PIPA-treated RBC units could further increase the metabolic benefits of RCE in SCA patients. STUDY DESIGN AND METHODS Circulating plasma and erythrocytes were collected from patients with SCA before and after RCE, with either conventional or PIPA-treated RBC units, prior to metabolomics analyses. RESULTS Consistent with prior work, RCE significantly decreased circulating levels of markers of systemic hypoxemia (lactate, succinate) and decreased plasma levels of acyl-carnitines and amino acids. However, PIPA-treated exchanges were superior to untreated RCEs, with a higher energy state and an increased capacity to activate the pentose phosphate pathway and glutamine metabolism. In addition, RBCs and plasma from recipients of PIPA-treated RBC units resulted in significantly decreased levels of post-transfusion plasticizers, though at the expense of higher circulating levels of oxidized purines (hypoxanthine, xanthine, and the antioxidant urate). CONCLUSION Transfusion of PIPA-treated RBCs further increases the metabolic benefits of RCE to patients with SCA, significantly reducing the levels of post-transfusion plasticizers.