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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL013754-20
Application #
3334696
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1989-09-15
Project End
1992-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
20
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Salzman, E W; Weinstein, M J; Reilly, D et al. (1993) Adventures in hemostasis. Desmopressin in cardiac surgery. Arch Surg 128:212-7
Penny, W F; Weinstein, M; Salzman, E W et al. (1991) Correlation of circulating von Willebrand factor levels with cardiovascular hemodynamics. Circulation 83:1630-6
Gerhart, T N; Yett, H S; Robertson, L K et al. (1991) Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial. J Bone Joint Surg Am 73:494-502
Weinstein, M; Ware, J A; Troll, J et al. (1988) Changes in von Willebrand factor during cardiac surgery: effect of desmopressin acetate. Blood 71:1648-55
Salzman, E W; McManama, G P; Shapiro, A H et al. (1987) Effect of optimization of hemodynamics on fibrinolytic activity and antithrombotic efficacy of external pneumatic calf compression. Ann Surg 206:636-41
Salzman, E W; Weinstein, M J; Weintraub, R M et al. (1986) Treatment with desmopressin acetate to reduce blood loss after cardiac surgery. A double-blind randomized trial. N Engl J Med 314:1402-6
Bertele, V; Stemerman, M; Schafer, A et al. (1985) Refractoriness of platelets to prostaglandins after infusion in rabbits. J Lab Clin Med 106:551-61
Lewis, J; Sweeney, J; Baldini, L et al. (1985) Assessment of thromboresistance of intravenous cannulae by 125I-fibrinogen scanning. J Biomed Mater Res 19:99-113