D'Alessandro Angelo, Reisz Julie A, Culp-Hill Rachel, Korsten Herbert, van Bruggen Robin, de Korte Dirk
Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.
Department of Product and Process Development, Sanquin Blood Bank, Amsterdam, the Netherlands.
Transfusion. 2018 Aug;58(8):1992-2002. doi: 10.1111/trf.14620. Epub 2018 Apr 6.
Over a century of advancements in the field of additive solutions for red blood cell (RBC) storage has made transfusion therapy a safe and effective practice for millions of recipients worldwide. Still, storage in the blood bank results in the progressive accumulation of metabolic alterations, a phenomenon that is mitigated by storage in novel storage additives, such as alkaline additive solutions. While novel alkaline additive formulations have been proposed, no metabolomics characterization has been performed to date.
We performed UHPLC-MS metabolomics analyses of red blood cells stored in SAGM (standard additive in Europe), (PAGGSM), or alkaline additives SOLX, E-SOL 5 and PAG3M for either 1, 21, 35 (end of shelf-life in the Netherlands), or 56 days.
Alkaline additives (especially PAG3M) better preserved 2,3-diphosphoglycerate and adenosine triphosphate (ATP). Deaminated purines such as hypoxanthine were predictive of hemolysis and morphological alterations. Guanosine supplementation in PAGGSM and PAG3M fueled ATP generation by feeding into the nonoxidative pentose phosphate pathway via phosphoribolysis. Decreased urate to hypoxanthine ratios were observed in alkaline additives, suggestive of decreased generation of urate and hydrogen peroxide. Despite the many benefits observed in purine and redox metabolism, alkaline additives did not prevent accumulation of free fatty acids and oxidized byproducts, opening a window for future alkaline formulations including (lipophilic) antioxidants.
Alkalinization via different strategies (replacement of chloride anions with either high bicarbonate, high citrate/phosphate, or membrane impermeant gluconate) results in different metabolic outcomes, which are superior to current canonical additives in all cases.
在红细胞（RBC）储存的添加剂解决方案领域，经过一个多世纪的发展，输血治疗已成为全球数百万受血者安全有效的治疗方法。尽管如此，在血库中的储存仍会导致代谢改变的逐渐积累，而在新型储存添加剂（如碱性添加剂溶液）中储存可缓解这一现象。虽然已经提出了新型碱性添加剂配方，但迄今为止尚未进行代谢组学表征。
我们对储存在SAGM（欧洲标准添加剂）、（PAGGSM）或碱性添加剂SOLX、E-SOL 5和PAG3M中的红细胞进行了超高效液相色谱-质谱代谢组学分析，储存时间分别为1天、21天、35天（荷兰保质期结束）或56天。
碱性添加剂（尤其是PAG3M）能更好地保存2,3-二磷酸甘油酸和三磷酸腺苷（ATP）。次黄嘌呤等脱氨基嘌呤可预测溶血和形态改变。在PAGGSM和PAG3M中添加鸟苷，通过磷酸核糖解作用进入非氧化戊糖磷酸途径，促进了ATP的生成。在碱性添加剂中观察到尿酸与次黄嘌呤的比率降低，提示尿酸和过氧化氢的生成减少。尽管在嘌呤和氧化还原代谢方面观察到许多益处，但碱性添加剂并不能阻止游离脂肪酸和氧化副产物的积累，这为未来包括（亲脂性）抗氧化剂在内的碱性配方打开了一扇窗。
通过不同策略（用高碳酸氢盐、高柠檬酸盐/磷酸盐或膜不透性葡萄糖酸盐替代氯离子）进行碱化会导致不同的代谢结果，在所有情况下均优于当前的标准添加剂。
