Effects of red blood cell (RBC) transfusion on sickle cell disease recipient plasma and RBC metabolism.
Effects of red blood cell (RBC) transfusion on sickle cell disease recipient plasma and RBC metabolism.
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DOI：
10.1111/trf.14931
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发表时间：
2018-12
期刊：
影响因子：
2.9
通讯作者：
D'Alessandro A
中科院分区：
文献类型：
--
作者：
Culp-Hill R;Srinivasan AJ;Gehrke S;Kamyszek R;Ansari A;Shah N;Welsby I;D'Alessandro A
交换输血是治疗镰状细胞性贫血的主要方法。镰状细胞受体每次治疗可以输注超过10个单位，这是一种用供体RBC替代循环镰状红细胞（RBC）的干预措施。RBC的储存使得干预在后勤上可行。在杜克大学医学中心输血单位的平均储存持续时间约为两周，这是一个可以预测红细胞不可逆储存损伤累积的时间窗。然而，迄今为止还没有进行代谢组学研究来调查交换输血对受者血浆和红细胞表型的影响。在进行代谢组学分析之前，在输血前和换血后5小时内（最多11个单位）从镰状细胞患者中采集血浆和红细胞。交换输血显著降低了全身性低氧血症标志物如乳酸、琥珀酸、1-磷酸鞘氨醇和2-羟基戊二酸的血浆水平。这些代谢物在输注的RBC中积累，表明RBC可充当清除剂/储库。输注的RBC显示出较高的糖酵解、总腺苷酸池和DPG，这与输送氧气的能力增加一致。血浆酰基-肉毒碱和氨基酸水平下降，而脂肪酸和潜在有害的邻苯二甲酸酯增加后，交换输血。代谢表型证实了镰状细胞接受者中输血治疗的益处以及两周龄RBC体内输血后一些代谢储存损伤的可逆性。然而，结果也表明，潜在的有害增塑剂是输血。
Exchange transfusion is a mainstay in the treatment of sickle cell anemia. Sickle cell recipients can be transfused over 10 units per therapy, an intervention that replaces circulating sickle red blood cells (RBCs) with donor RBCs. Storage of RBCs makes the intervention logistically feasible. The average storage duration for units transfused at the Duke University Medical Center is ~two weeks, a time window that should anticipate the accumulation of irreversible storage lesion to the erythrocyte. However, no metabolomics study has been performed to date to investigate the impact of exchange transfusion on recipients’ plasma and red blood cell phenotypes. Plasma and red blood cells were collected from sickle cell patients before transfusion and within 5h from exchange transfusion with up to 11 units, prior to metabolomics analyses. Exchange transfusion significantly decreased plasma levels of markers of systemic hypoxemia like lactate, succinate, sphingosine 1-phosphate and 2-hydroxyglutarate. These metabolites accumulated in transfused RBCs, suggesting that RBCs may act as scavenger/reservoirs. Transfused RBCs displayed higher glycolysis, total adenylate pools and DPG, consistent with increased capacity to deliver oxygen. Plasma levels of acyl-carnitines and amino acids decreased, while fatty acids and potentially harmful phthalates increased upon exchange transfusion. Metabolic phenotypes confirm the benefits of the transfusion therapy in sickle cell recipients and the reversibility of some of the metabolic storage lesion upon transfusion in vivo in two-week-old RBCs. However, results also suggest that potentially harmful plasticizers are transfused.
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