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NHLBI Working Group Translational and Clinical Research in Thrombosis and Hemostasis
Executive SummaryOn June 19, 2009, the National Heart, Lung and Blood Institute convened a Working Group of expert scientists and clinicians to discuss the status of translational and clinical research in thrombosis and hemostasis and identify research priorities. The group also evaluated the current SCCOR program for its ability to address the needs of the research community. Dr. Keith Hoots, Director of the Division of Blood Diseases and Resources, welcomed the participants and requested their advice and recommendations in advancing translational and clinical research. Background:Most Americans at some time will be afflicted by a thrombotic disease or will receive treatment to prevent thrombosis. Thrombosis is the critical event in myocardial infarction and stroke, and antithrombotic agents are widely used for preventive therapy in high risk populations. Thromboembolic stroke is a dreaded complication for the growing number of patients with atrial fibrillation. There is significant risk of venous thrombosis and pulmonary embolism associated with many orthopedic procedures, and it is a serious complication of diabetes, metabolic syndrome, sickle cell disease, hereditary diseases of the clotting system, pulmonary arterial hypertension, bone marrow disorders, and certain cancers, especially in the context of an aging population. Maintaining hemostatic control and treatment of bleeding events is a challenge for hereditary and nonhereditary bleeding disorders such as hemophilia and platelet disorders. Acquired bleeding states represent a major complication of trauma, gastrointestinal ulcers and drugs used to treat and prevent thrombosis. Hemorrhagic stroke can be the fatal result of high blood pressure, aneurysms, arterovenous malformation or medications. Research is needed to better understand the mechanisms of thrombosis and hemorrhage, and the regulatory systems that normally maintain the balance between the two. This could also lay the groundwork for development of safer anti-thrombotic therapies and their efficacious use. Currently available knowledge and tools to assess an individual’s risk in a particular situation, or response to hemostatic or antithrombotic therapy can lead to over-treatment of some and under-treatment of others. A better understanding of human mechanisms and improved laboratory analysis are required to enable personalized clinical management. Multi-disciplinary teams are needed to determine the impact of hemostatic and thrombotic mechanisms in the pathology of diverse disease entities and clinical conditions, develop efficient, cost effective diagnostic tools, and improve clinical options to treat and prevent thrombotic or bleeding events. Translational and clinical research topics:The potential topics for translational and clinical research in thrombosis and hemostasis were considered to be broad and diverse. The greatest impact on moving the field forward would be achieved by bringing together basic, translational and clinical investigators with varied expertise to address hemostatic and thrombotic problems and questions. The following areas were discussed, but it was recognized that there are many other important challenges in thrombosis and hemostasis.
Training of the next generation of investigators:Training programs are needed to ensure that there will be a next generation of hemostasis/thrombosis research investigators. These programs should include cross-training between clinical and basic research for all levels of investigators, and between scientists in different clinical disciplines. There is a critical need for experimental medicine investigators doing patient-based studies in non-malignant hematology. The training program should interact with other existing programs such as Clinical and Translational Science Awards, Career Development (K) Awards, and institutional training grants and programs. The scientific environment in a productive translational and clinical research program could be an ideal setting for inspiring and training future translational investigators. Recommendations:A strong integrated program is required to address the translational and clinical research needs in thrombosis and hemostasis. An effective multi-disciplinary approach cannot be accomplished with investigator initiated programs alone. Therefore a new program should be developed that would relate mechanistic studies to human physiology and pathology. Because of the scale and scope of the clinical problem and the potential impact of a translational and clinical research program, ten centers are recommended. The new expanded program should include increased interaction of participating investigators and an effective training component. Suggested program characteristics include:
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