RELEASABLE PLATELET PLASMINOGEN ACTIVATOR-INHIBITOR

静脉血栓栓塞和深静脉血栓性静脉炎是引起血栓性静脉炎的主要原因

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.