This is a competing renewal application for support of a series of controlled prospective clinical trials with related laboratory investigations into the pathophysiology of thrombotic states and related conditions and the pharmacology of new antithrombotic and hemostatic drugs. The specific trials to be conducted will be the following: 1. A trial of the prevention of venous thromboembolism in elderly patients with fractures of the hip by administration of the heparin-like compound Organon 10172; 2. An exploration of the-ability of DDAVP to improve hemostasis in pediatric patients undergoing cardiopulmonary bypass for treatment of congenital heart disease; 3. An examination of the effect of DDAVP on blood loss in the perioperative period in patients undergoing total hip replacement. In this study, the possibility that DDAVP may induce a prothrombotic state in postoperative patients will be investigated by screening the patients for the development of postoperative venous thrombosis by labelled fibrinogen scanning and impedance plethysmography; 4. A trial of activated recombinant protein C as an antithrombotic agent in patients at high risk of developing postoperative venous thromboembolism: specifically, an investigation of the efficacy and safety of the intraoperative and postoperative infusion of the protein prepared by recombinant DNA techniques for the prevention of venous thrombosis in patients undergoing total hip replacement, employing phlebography for diagnosis. In those studies involving DDAVP, the mechanism by which it achieves an improvement in hemostasis will be, sought by measurement of the quantity, quality, and activity of factor VIII: von Willebrand's factor, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1). These studies will be performed in the laboratory of Dr. Mark Weinstein at Boston University.
