Sodium citrate contributes to the platelet storage lesion
Sodium citrate contributes to the platelet storage lesion
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DOI：
10.1111/trf.15213
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发表时间：
2019-06-01
期刊：
影响因子：
2.9
通讯作者：
Wagner, Stephen J.
中科院分区：
文献类型：
--
作者：
Getz, Todd M.;Turgeon, Annette;Wagner, Stephen J.
背景柠檬酸钠已成为单采术采集的首选抗凝剂，自PAS-II以来已被纳入市售血小板添加剂溶液（PAS）中。建议在PAS中加入柠檬酸盐以防止自发聚集。细胞系和脐带血中的报告已经证明PAS制剂中存在的柠檬酸盐浓度（10 mM）会导致细胞凋亡。我们评估了从PAS-III中去除柠檬酸盐是否可以改善血小板储存。研究设计和方法研究1评价了柠檬酸盐剂量反应对血小板在含有氯化钠、乙酸钠和磷酸盐的65% PAS中储存的影响。研究2比较了储存在65%无柠檬酸盐PAS-III或含10 mM柠檬酸盐PAS-III中的血小板的细胞质量和功能。测量包括细胞计数、血气、表面活化标志物的流式细胞术分析和聚集。结果研究1确定，PAS中包含柠檬酸盐导致葡萄糖利用、乳酸盐形成、P-选择素表达、磷脂酰丝氨酸（PS）暴露和活性氧（ROS）形成的剂量依赖性增加。研究2显示了类似的结果，其中与含柠檬酸盐的PAS-III相比，储存在不含柠檬酸盐的PAS-III中的血小板通过更好地维持葡萄糖利用而受益，乳酸产生、P-选择素表达、PS暴露和ROS形成更少。储存在无柠檬酸盐PAS-III中的血小板的聚集反应比储存在PAS-III中的血小板至少高10%。结论：在无柠檬酸盐PAS-III中储存单采血小板改善了多个储存参数，包括葡萄糖利用、乳酸产生、P-选择素表达、PS暴露和ROS形成，并导致聚集适度增加。
BACKGROUND Sodium citrate has become the preferred anticoagulant used for apheresis collection and has been included in commercial platelet additive solutions (PASs) since PAS-II. It was suggested that citrate be included in PASs to prevent spontaneous aggregation. Reports in cell lines and cord blood have demonstrated that concentrations of citrate present in PAS formulations (10 mM) cause apoptosis. We evaluated whether the removal of citrate from PAS-III could improve platelet storage. STUDY DESIGN AND METHODS Study 1 evaluated the effects of a citrate dose response on the storage of platelets in 65% PAS containing sodium chloride, sodium acetate, and phosphate. Study 2 compared the cell quality and function of platelets stored in 65% citrate-free PAS-III or PAS-III containing 10 mM of citrate. Measurements included cell count, blood gases, flow cytometry analysis of surface activation markers, and aggregation. RESULTS Study 1 identified that inclusion of citrate in PAS resulted in a dose-dependent increase in glucose utilization, lactate formation, P-selectin expression, phosphatidylserine (PS) exposure, and reactive oxygen species (ROS) formation. Study 2 showed similar results in which platelets stored in citrate-free PAS-III benefited through better maintenance of glucose utilization with less lactate production, P-selectin expression, PS exposure, and ROS formation compared to citrate-containing PAS-III. Platelets stored in citrate-free PAS-III had aggregation responses that were at least 10% greater than those platelets stored in PAS-III. CONCLUSION Storage of apheresis platelets in citrate-free PAS-III improved multiple storage parameters including glucose utilization, lactate production, P-selection expression, PS exposure, and ROS formation and resulted in a modest increase in aggregation.