Calcium Ion Chelation Preserves Platelet Function During Cold Storage.
Calcium Ion Chelation Preserves Platelet Function During Cold Storage.
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DOI：
10.1161/atvbaha.120.314879
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Li Z
中科院分区：
文献类型：
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作者：
Xiang B;Zhang G;Zhang Y;Wu C;Joshi S;Morris AJ;Ware J;Smyth SS;Whiteheart SW;Li Z
血小板输注是预防或治疗血小板减少或血小板功能障碍患者出血的一种救命疗法。然而，六十多年来，安全有效的血小板储存策略一直阻碍着血小板输注的广泛应用。冷藏的血小板迅速从循环中清除，避免了用于输血的血小板的冷藏。因此，由于细菌污染和血小板功能丧失的风险，血小板储存在室温(RT)中，上限为5天。这种做法严重限制了可供输注的血小板。本研究旨在探讨冷藏后血小板清除的机制，并建立一种血小板冷藏方法。我们发现，冷藏血小板的快速清除在很大程度上是由于整合素的激活和细胞凋亡。整合素半胱氨酸酶3或半胱氨酸天冬氨酸氨基转移酶-3的缺失延长了冷藏血小板在循环中的时间。用EGTA(一种细胞不透性的钙离子螯合剂)对血小板进行预处理，可逆转地抑制冷藏诱导的血小板活化，从而延长冷藏血小板的循环。此外，向糖蛋白Ibα缺乏的小鼠输注经EGTA处理的冷藏血小板，但不输注RT储存的血小板，显著缩短了尾部出血时间，减少了失血。整合素的激活和凋亡是血小板冷藏后快速清除的潜在机制。在血小板制品中添加细胞不透性的钙离子螯合剂可能是一种简单而有效的方法来冷藏供输血的血小板。
Platelet transfusion is a life-saving therapy to prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. However, for more than six decades, safe and effective strategies for platelet storage have been an impediment to widespread use of platelet transfusion. Refrigerated platelets are cleared rapidly from circulation, precluding cold storage of platelets for transfusion. Consequently, platelets are stored at room temperature (RT) with an upper limit of 5 days due to risks of bacterial contamination and loss of platelet function. This practice severely limits platelet availability for transfusion. This study is to identify the mechanism of platelet clearance after cold storage and develop a method for platelet cold storage. We found that rapid clearance of cold-stored platelets was largely due to integrin activation and apoptosis. Deficiency of integrin β3 or caspase-3 prolonged cold-stored platelets in circulation. Pre-treatment of platelets with EGTA, a cell impermeable calcium ion chelator, reversely inhibited cold storage-induced platelet activation and consequently prolonged circulation of cold-stored platelets. Moreover, transfusion of EGTA-treated, cold-stored platelets, but not RT-stored platelets, into the mice deficient in glycoprotein Ibα significantly shortened tail-bleeding times and diminished blood loss. Integrin activation and apoptosis is the underlying mechanism of rapid clearance of platelets after cold storage. Addition of a cell impermeable calcium ion chelator to platelet products is potentially a simple and effective method to enable cold storage of platelets for transfusion.