Drs. Key and Mackman received their grant from the National Heart, Lung, and Blood Institute. Dr. Key, Harold Roberts Distinguished Professor of Medicine, and Dr. Mackman, John C. Parker Distinguished Professor of Medicine, will serve as joint principal investigators on the grant.
Venous thromboembolism (VTE) is a leading cause of disability and death in cancer patients. The incidence of VTE in these patients is further increased by the administration of anti-cancer drugs. However, the mechanisms of VTE in cancer patients are largely unknown.
The overall goal of this proposal is to determine whether an association exists between levels of a procoagulant molecule called tissue factor in the circulation and venous thrombosis in patients with pancreatic or colon cancer, and in tumor-bearing mice. The general hypothesis is that cancer and chemotherapy drugs increase the release of tissue factor-positive microparticles (small membrane vesicles released from activated or apoptotic cells) into the circulation which increases the risk of thrombosis. The study will determine if levels of tissue factor-positive microparticles can be used as a biomarker of a pre-thrombotic state in patients with pancreatic or colon cancer. This will be a multi-center prospective observational study utilizing patient blood samples from the University of North Carolina at Chapel Hill, East Carolina University and Rex Hospital. In addition, mouse models will be used to directly examine the role of tissue factor-positive microparticles in venous thrombosis.