RELEASABLE PLATELET PLASMINOGEN ACTIVATOR-INHIBITOR

静脉血栓栓塞和深静脉血栓性静脉炎是引起 术后发病率和死亡率。 由于种种原因，历史 体格检查、静脉内静脉造影和I-125碘摄入量是 要么不够可靠，要么有太多与风险相关的侵入性， 用于DVT的筛查，尤其是在可疑的情况下。 也不 是否有明确的，具体的风险因素，可以确定为 使手术患者易于发生血栓形成 并发症 本研究的长期目标是确定可能的作用 释放性血小板纤溶酶原激活物抑制剂（PA抑制剂） 术后血栓形成的发展，并制定一个功能 PA抑制剂的测定，其可用于跟踪术后 血浆PA抑制剂水平的变化。 达到这些目标的具体目标是：1）在一个 使用凝集素亲和力的天然形式的可释放的血小板PA抑制剂， HPLC柱色谱法; 2）表征这种相互作用 纯化的PA-抑制剂与其他血小板释放蛋白， 免疫沉淀法和SDS-凝胶法测定纤维蛋白原或血小板反应蛋白 电泳，并确定这些相互作用是否是重要的 改变纤溶酶原激活剂的抑制动力学，和/或 活化蛋白C;和，3）开发血浆的功能测定 PA-抑制剂水平基于用尿激酶代替 抗体，并使用该测定法来跟踪 PA抑制剂水平。 这项研究的结果可以提供基础， 对于更广泛的应用， PA抑制剂水平与术后深静脉血栓形成

Venous thrombo-embolism and deep vein thrombophlebitis are major causes of post-surgical morbidity and mortality. For a variety of reasons, history and physical exam, intravenous phlebography, and I-125 iodine uptake are either not reliable enough or have too much risk-associated invasiveness to be used in the screening for DVT, especially in equivocal situations. Nor are there well-identified, specific risk factors one can determine as predisposing the surgical patient toward developing thrombotic complications. The long-term objectives of this study are to determine the possible roles of releasable platelet plasminogen activator-inhibitor (PA-inhibitor) in the post-surgical development of thrombosis and to develop a functional assay for the PA-inhibitor which could be used to follow the post-surgical changes in plasma PA-inhibitor levels. Specific aims toward meeting these objectives are to: 1) purify in a native form the releasable platelet PA-inhibitor using lectin affinity and HPLC column chromatography; 2) characterize the interaction of this purified PA-inhibitor with other platelet releasate proteins such as fibrinogen or thrombospondin by imunoprecipitation and SDS-gel electrophoresis and determine whether these interactions are important in modifying the kinetics of inhibition of plasminogen activators and/or activated protein C; and, 3) develop a functional assay of plasma PA-inhibitor levels based on ELISA plates coated with urokinase in place of antibodies and to use this assay to follow the post-surgical kinetics of PA-inhibitor levels. The results from this studies could provide the basis for a more extensive application to correlate elevated functional PA-inhibitor levels with post-surgical deep vein thrombosis.