Antioxidant prevents clearance of hemostatically competent platelets after long-term cold storage.

Antioxidant prevents clearance of hemostatically competent platelets after long-term cold storage.
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抗氧化剂可防止长期冷藏后止血活性血小板的清除。

DOI:
10.1111/trf.16200
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发表时间:
2021-03
期刊:
影响因子:
2.9
通讯作者:
Cancelas JA
Cancelas JA
中科院分区:
医学3区
文献类型:
--
作者:
Hegde S;Wellendorf AM;Zheng Y;Cancelas JA

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鉴于储存期间细菌生长的可能性降低,并且可能对治疗出血患者产生有益效果,血小板(PLT)的冷藏具有延长储存时间、同时减少输血后感染的潜在优势。然而,冷藏会引起复杂的储存损伤,从而降低 PLT 的存活率,当储存时间延长时,这种损伤会更加严重。来自七个 PLT 池的全血富含 PLT 血浆浓缩物(每个池 n = 5 名供体)。添加 PLT 添加剂溶液(67%/33% 血浆)并将产品分装到 50 mL 袋中。在室温或寒冷条件下,在存在或不存在 1 mM N-乙酰半胱氨酸 (NAC) 的情况下,将分割单元保存长达 14 天,并分析 PLT 激活、纤维蛋白原依赖性扩散、微粒形成、线粒体呼吸活性、活性氧 (ROS) 生成,以及免疫缺陷患者的体内存活和出血时间校正 老鼠。 PLT 冷藏 7 天或更长时间会诱导显着的 PL​​T 激活、细胞骨架损伤、纤维蛋白原扩散受损、增强线粒体代谢解偶联和 ROS 生成,并增加巨噬细胞依赖性吞噬作用和巨噬细胞非依赖性清除作用。添加 NAC 可防止 PLT 清除,并可纠正接受阿司匹林治疗的血小板减少、免疫缺陷小鼠的出血时间延长。长期冷藏会诱导线粒体解偶联,增加质子泄漏和活性氧生成。由此产生的 ROS 对功能性 PLT 的巨噬细胞依赖性和非依赖性清除增加至关重要,并且可以通过含镁添加剂溶液中的抗氧化剂 NAC 来预防。
Cold storage of platelets (PLTs) has the potential advantage of prolonging storage time while reducing posttransfusion infection given the decreased likelihood of bacterial outgrowth during storage and possibly beneficial effects in treating bleeding patients. However, cold storage reduces PLT survival through the induction of complex storage lesions, which are more accentuated when storage is prolonged. Whole blood–derived PLT-rich plasma concentrates from seven PLT pools (n = 5 donors per pool). PLT additive solution was added (67%/33% plasma) and the product was split into 50-mL bags. Split units were stored in the presence or absence of 1 mM of N-acetylcysteine (NAC) under agitation for up to 14 days at room temperature or in the cold and were analyzed for PLT activation, fibrinogen-dependent spreading, microparticle formation, mitochondrial respiratory activity, reactive oxygen species (ROS) generation, as well as in vivo survival and bleeding time correction in immunodeficient mice. Cold storage of PLTs for 7 days or longer induces significant PLT activation, cytoskeletal damage, impaired fibrinogen spreading, enhances mitochondrial metabolic decoupling and ROS generation, and increases macrophage-dependent phagocytosis and macrophage-independent clearance. Addition of NAC prevents PLT clearance and allows a correction of the prolonged bleeding time in thrombocytopenic, aspirin-treated, immunodeficient mice. Long-term cold storage induces mitochondrial uncoupling and increased proton leak and ROS generation. The resulting ROS is a crucial contributor to the increased macrophage-dependent and -independent clearance of functional PLTs and can be prevented by the antioxidant NAC in a magnesium-containing additive solution.
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