Snyder E, Perrotta P, Rinder H, Baril L, Nichol J, Gilligan D
Blood Bank and the Department of Laboratory Medicine, Yale University School of Medicine, Yale-New Haven Hospital, Connecticut 06504, USA.
Transfusion. 1999 Mar;39(3):258-64. doi: 10.1046/j.1537-2995.1999.39399219281.x.
Platelet production is regulated by a thrombopoietic growth factor (Mpl ligand). The receptor for this platelet growth factor (Mpl) is expressed on the platelet surface membrane. A recombinant thrombopoietic cytokine, recombinant human megakaryocyte growth and development factor coupled with polyethylene glycol (PEG-rHuMGDF), was added to apheresis platelets in vitro to determine whether Mpl ligand-receptor binding produced any beneficial or adverse effect on the development of the platelet storage lesion during 5 days of storage.
This study was designed as a dose-response protocol to determine the effects of adding increasing concentrations of PEG-rHuMGDF (0.0 [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored in two types of plastic storage containers. The increasing concentrations of PEG-rHuMGDF used simulated the theoretical peak plasma level attained in vivo, with an intravenous dose of 0, 0.1, 1.0 and 10 microg per kg of PEG-rHuMGDF. The platelets were stored with agitation at 20 to 24 degrees C for 5 days. A battery of in vitro assays was performed on storage Days 1 and 5, including pH, blood gases, platelet count, lactate dehydrogenase, mean platelet volume, glucose, lactate, osmotic recovery, morphology score, CD62P, and one-dimensional polyacrylamide gel electrophoresis analyses.
Analysis of results on both Day 1 and Day 5 showed no significant differences among any of the three PEG-rHuMGDF doses and the control group, for any in vitro assay. One-dimensional polyacrylamide gel electrophoresis showed no changes among the platelet protein patterns for the three PEG-rHuMGDF doses studied or the control. Storage-induced changes, however, did occur equally in all four groups of platelets over the 5 days of storage.
The addition to stored apheresis platelets of up to 10 microg per kg of PEG-rHuMGDF (250 ng/mL), followed by 5 days of storage at standard conditions, does not appear to promote or retard development of the platelet storage lesion.
血小板生成受血小板生成生长因子（Mpl配体）调控。这种血小板生长因子的受体（Mpl）表达于血小板表面膜上。将重组血小板生成细胞因子，即聚乙二醇偶联的重组人巨核细胞生长发育因子（PEG-rHuMGDF），在体外添加至单采血小板中，以确定Mpl配体-受体结合在储存5天期间对血小板储存损伤的发展是否产生任何有益或不良影响。
本研究设计为剂量反应方案，以确定向储存在两种类型塑料储存容器中的单采血小板添加递增浓度的PEG-rHuMGDF（0.0[对照]、2.5、25和250 ng/mL）的效果。所使用的递增浓度的PEG-rHuMGDF模拟了静脉注射0、0.1、1.0和10 μg/kg PEG-rHuMGDF时体内达到的理论血浆峰值水平。血小板在20至24℃搅拌下储存5天。在储存第1天和第5天进行了一系列体外检测，包括pH值、血气、血小板计数、乳酸脱氢酶、平均血小板体积、葡萄糖、乳酸、渗透恢复、形态学评分、CD62P以及一维聚丙烯酰胺凝胶电泳分析。
第1天和第5天的结果分析表明，对于任何体外检测，三种PEG-rHuMGDF剂量组与对照组之间均无显著差异。一维聚丙烯酰胺凝胶电泳显示，所研究的三种PEG-rHuMGDF剂量组或对照组的血小板蛋白质模式均无变化。然而，在5天的储存期内，所有四组血小板中均同样发生了储存诱导的变化。
向储存的单采血小板中添加高达10 μg/kg的PEG-rHuMGDF（250 ng/mL），随后在标准条件下储存5天，似乎不会促进或延缓血小板储存损伤的发展。
