BLOOD BANK IMMUNODIAGNOSTICS FOR PLATELET PROTEINS

在接下来的一年里，美国将有超过4 百万单位血小板输注用于各种医疗 原因 尽管有大量的知识， 血小板的生理生化、本血的功效 产品在纠正出血问题方面通常是 根据血小板计数和出血时间测定， 这两者都只能在血小板 被输血了。 体内疗效差和生存率相关 在此之前血小板已经被激活的程度 输血。 在过去的几年里，一些小说 已经描述了血小板蛋白，其仅在 活化的血小板表面。 一种这样的蛋白质PADGEM或 GMP-140蛋白存在于α颗粒中， 在血小板表面表达， 被激活以表达其生化潜能， 参与止血。 我们建议发展一个快速的 体外血小板活化免疫诊断试验 储存，将测量PADGEM/GMP-140的表面上 血小板在一段时间内，这个细胞是储存在塑料 输血前的袋子。 在第一阶段的研究中，我们将确定 这种蛋白质在血小板上出现的动力学 储存期间的表面与已知的 血小板活化的生化标志物和体内 这个细胞的生存。 如果我们能证明 这两个观察，我们将在第二阶段进行格式 血小板表面上PADGEM/GMP-140合适免疫测定 供血库使用，并在 人类对这种测定在预测 输注血小板纠正出血缺陷的疗效。

During the next year in there United States there will be over 4 million units of platelets transfused for a variety of medical reasons. In spite of the remarkable body of knowledge about platelet physiology and biochemistry, efficacy of this blood product in terms of correcting bleeding problems is usually measured according to the platelet count and the bleeding time, both of which can be determined only after the platelets have been transfused. Poor in vivo efficacy and survival correlates with the extent to which the platelets have been activated prior to transfusion. Within the past few years a number of novel platelet proteins have been described which are only found on the surface of activated platelets. One such protein the PADGEM or the GMP-140 protein which is found in the alpha granules but is expressed on the surface of the platelet once this cell has been activated to express its biochemical potential in terms of participating in hemostasis. We are proposing to develop a rapid immunodiagnostic test fr platelet activation during in vitro storage that will measure PADGEM/GMP-140 on the surface of platelets over the time period which this cell is stored in a plastic bag prior to transfusion. In this phase I study we will determine whether the kinetics of appearance of this protein on the platelet surface during storage correlates with the presence of known biochemical markers of platelet activation and the in vivo survival of this cell. If we can show there is correlation between these two observations, we will proceed in Phase II to format a suitable immunoassay for PADGEM/GMP-140 on platelet surfaces for use in the blood bank and to undertake full clinical trials in humans on the usefulness of this assay in terms of predicting the efficacy of transfused platelets to correct bleeding defects.