Key Alicia M, Earley Eric J, Tzounakas Vassilis L, Anastasiadi Alkmini T, Nemkov Travis, Stephenson Daniel, Dzieciatkowska Monika, Reisz Julie A, Keele Gregory R, Deng Xutao, Stone Mars, Kleinman Steve, Hansen Kirk C, Norris Philip J, Busch Michael P, Roubinian Nareg H, Page Grier P, D'Alessandro Angelo
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Department of Biostatistics and Epidemiology, RTI International, Research Triangle Park, North Carolina, USA.
Transfusion. 2025 Mar;65(3):560-574. doi: 10.1111/trf.18140. Epub 2025 Jan 19.
Storage of packed red blood cells (RBCs) for transfusion leads to biochemical and morphological changes, increasing hemolysis risk. Urate levels in blood bags at donation contribute to the molecular heterogeneity and hemolytic propensity of stored RBCs. However, studies to date have been underpowered to investigate at scale the contribution of donor demographics and genetics to the heterogeneity in urate levels across donations.
Urate levels were measured in 13,091 RBC units from the REDS study. Characteristics tested included hemolysis parameters (spontaneous, osmotic, oxidative) at storage end and post-transfusion hemoglobin (Hb) increments in recipients. Donor demographics, urate levels, and genetic variants were analyzed for associations with these outcomes.
Elevated urate levels were linked to male sex, older age, high BMI, and Asian descent. Units with high urate levels exhibited increased spontaneous and osmotic hemolysis, while oxidative hemolysis was unaffected. Genetic variants in SLC2A9 (V282I) and ABCG2 (Q141K) were strongly associated with elevated urate, particularly in Asian donors. Post-transfusion analyses revealed that units from female donors carrying these variants were associated with reduced Hb increments, with up to a 31% reduction in efficacy. This effect was not observed in male donors.
RBC urate levels and genetic traits significantly impact storage quality and transfusion outcomes. These findings highlight the importance of donor molecular characteristics for optimizing transfusion strategies. Moreover, genetic and metabolic insights may inform donor recruitment efforts, providing health feedback to volunteers while ensuring effective transfusion products.
用于输血的浓缩红细胞（RBC）储存会导致生化和形态学变化，增加溶血风险。献血时血袋中的尿酸水平会导致储存的RBC出现分子异质性和溶血倾向。然而，迄今为止的研究在大规模调查供者人口统计学和遗传学对不同献血中尿酸水平异质性的贡献方面能力不足。
对REDS研究中13091个RBC单位的尿酸水平进行了测量。测试的特征包括储存末期的溶血参数（自发、渗透、氧化）以及受血者输血后血红蛋白（Hb）增加量。分析了供者人口统计学、尿酸水平和基因变异与这些结果之间的关联。
尿酸水平升高与男性、年龄较大、高体重指数和亚洲血统有关。尿酸水平高的单位自发溶血和渗透溶血增加，而氧化溶血不受影响。SLC2A9（V282I）和ABCG2（Q141K）基因变异与尿酸升高密切相关，尤其是在亚洲供者中。输血后分析显示，携带这些变异的女性供者的单位与Hb增加量减少有关，疗效降低高达31%。在男性供者中未观察到这种效应。
RBC尿酸水平和遗传特征显著影响储存质量和输血结果。这些发现凸显了供者分子特征对优化输血策略的重要性。此外，遗传和代谢方面的见解可能为供者招募工作提供信息，可以在确保输血产品有效的同时，为志愿者提供健康反馈。
