The goal of this SCOR application is to identify and characterize key risk factors for thrombosis that will improve methods for its prevention and treatment. The SCOR is specifically designed to promote synergy between basic and clinical research. It includes a randomized, prospective clinical trial to address the optimal duration of oral anticoagulant therapy for venous thrombosis (Project 1), a physiological study of the role of IL-6 in augmenting thrombosis (Project 4), and biochemical projects that examine the role of phospholipids and anti- phospholipid antibodies in the protein C pathway (Project 2), the membrane requirements for the tissue factor/factor VII pathway (Project 3), and the role of cytokines and other mediators in regulating the expression of P-selectin (Project 5). There is significant overlap in the scientific goals of the laboratory-based projects. In addition, an essential link for all SCOR components is the Assay Core, which will perform coagulation, ELISA, and DNA assays on blood samples from the patients in Project 1. The data from these assays will help answer mechanistic questions in the laboratory-oriented projects, which, in turn, will help define specific risk factors for recurrent thrombosis in the patients of Project 1. The SCOR is organized to facilitate generation and testing of hypotheses that will move between the basic and clinical arenas. The long-term objective is better understand the etiology of thrombosis, thereby allowing design of better treatment strategies.
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