Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Transfusion. 2021 Feb;61(2):557-567. doi: 10.1111/trf.16200. Epub 2020 Nov 27.
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.
由于在储存过程中细菌生长的可能性降低，并且在治疗出血患者方面可能具有有益作用，冷藏血小板 (PLT) 具有延长储存时间的潜在优势。然而，冷藏通过诱导复杂的储存损伤来降低 PLT 的存活率，而当储存时间延长时，这种损伤会更加明显。
从七个 PLT 池的全血衍生的富含 PLT 的血浆浓缩物（每个池 5 个供体）。添加血小板添加剂溶液（67%/33%血浆），将产物分成 50 毫升袋。在室温或冷藏下，将分割的单位在搅拌下储存长达 14 天，存在或不存在 1mM 的 N-乙酰半胱氨酸 (NAC)，并分析 PLT 激活、纤维蛋白原依赖性扩展、微粒形成、线粒体呼吸活性、活性氧 (ROS) 生成以及免疫缺陷小鼠的体内存活和出血时间校正。
PLT 冷藏 7 天或更长时间会导致明显的 PLT 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和巨噬细胞非依赖性清除。添加 NAC 可防止 PLT 清除，并允许纠正血小板减少症、阿司匹林治疗、免疫缺陷小鼠的延长出血时间。
长期冷藏会诱导线粒体解偶联和质子漏增加以及 ROS 生成增加。由此产生的 ROS 是导致功能性 PLT 巨噬细胞依赖性和非依赖性清除增加的关键因素，并且可以在含有镁的添加剂溶液中的抗氧化剂 NAC 中预防。
