Uncontrolled hemorrhage is the major cause of death in adults exposed to severe trauma. Trauma induced coagulopathy (TIC) occurs after injury and shock, accompanied by a """"""""storm"""""""" of inflammatory and coagulation events leading to incapacitation of the hemostatic process. TICs compromise the hemostatic system because of dysregulated processes occurring on a systemic basis in which proteolytic systems destroy essential coagulation components. Previous studies have identified activated protein C-mediated destruction of the cofactor factor Va and implicated systemic fibrinolytic activity in which unregulated proteolysis destroys fibrinogen and parts of the plasma coagulation system. These terminal events observed in phlebotomy blood of TIC patients are caused by in vivo processes involving the proteins, cells and cytokines in blood and vascular tissues and tissue damage material entering the blood. The causes and breadth of TICs are not understood. This TACTIC proposal provides a comprehensive evaluation of the contributions of plasma proteins, blood cells, the vascular endothelium, the blood vessel, and extravascular tissue to TIC, making use of a unique infrastructure that includes already-funded DoD sites involved in trauma trials and Systems Biology. A comprehensive team approach by leading investigators in coagulation and inflammation research addresses the problem using a composite of in vitro and in vivo approaches to identify candidates responsible for TICs. Early translation of laboratory results into useful technology will be enabled by a set of 5 TACTIC trauma centers. Simultaneous with these studies, interactions with clinical centers engaged in DoD clinical trials will be developed in which research personnel at each center will be responsible for point-of-care studies and processing of blood samples. Collection techniques will utilize inhibitory cocktails to block ex vivo, post phlebotomy artifacts. Blood/plasma samples will be shipped to a secure repository and analyzed utilizing new technology to identify the natural history of TIC events. Continuation of TACTIC research projects will be dependent upon their potential utility for diagnosis and selection of therapy for trauma patients. Although uncontrolled bleeding is the major cause of death in people with severe traumatic injuries, the reasons for this bleeding are not completely understood. We plan to comprehensively describe the causes of trauma-related clotting and bleeding, and propose methods to diagnose the different causes and ultimately therapeutic interventions to prevent morbidity and mortality in traumatic settings.
Although uncontrolled bleeding is the major cause of death in people with severe traumatic injuries, the reasons for this bleeding are not completely understood. We plan to comprehensively describe the causes of trauma-related clotting and bleeding, and propose methods to diagnose the different causes and ultimately therapeutic interventions to prevent morbidity and mortality in traumatic settings.
|Ashar, Harshini K; Mueller, Nathan C; Rudd, Jennifer M et al. (2018) The Role of Extracellular Histones in Influenza Virus Pathogenesis. Am J Pathol 188:135-148|
|Shupp, Jeffrey W; Prior, Shannon M; Jo, Daniel Y et al. (2018) Analysis of factor XIa, factor IXa and tissue factor activity in burn patients. Burns 44:436-444|
|Nunns, Geoffrey R; Moore, Ernest E; Stettler, Gregory R et al. (2018) Empiric transfusion strategies during life-threatening hemorrhage. Surgery 164:306-311|
|Smith, Stephanie A; Wang, Yan; Morrissey, James H (2018) DNA ladders can be used to size polyphosphate resolved by polyacrylamide gel electrophoresis. Electrophoresis 39:2454-2459|
|Slaughter, Anne L; Nunns, Geoffrey R; D'Alessandro, Angelo et al. (2018) The Metabolopathy of Tissue Injury, Hemorrhagic Shock, and Resuscitation in a Rat Model. Shock 49:580-590|
|Shahzad, Khurrum; Gadi, Ihsan; Nazir, Sumra et al. (2018) Activated protein C reverses epigenetically sustained p66Shc expression in plaque-associated macrophages in diabetes. Commun Biol 1:104|
|Prior, Shannon M; Mann, Kenneth G; Freeman, Kalev et al. (2018) Continuous thrombin generation in whole blood: New applications for assessing activators and inhibitors of coagulation. Anal Biochem 551:19-25|
|Stettler, Gregory R; Sumislawski, Joshua J; Moore, Ernest E et al. (2018) Citrated kaolin thrombelastography (TEG) thresholds for goal-directed therapy in injured patients receiving massive transfusion. J Trauma Acute Care Surg 85:734-740|
|Coleman, Julia R; Moore, Ernest E; Chapman, Michael P et al. (2018) Rapid TEG efficiently guides hemostatic resuscitation in trauma patients. Surgery 164:489-493|
|Kornblith, Lucy Z; Robles, Anamaria J; Conroy, Amanda S et al. (2018) Perhaps it's not the platelet: Ristocetin uncovers the potential role of von Willebrand factor in impaired platelet aggregation following traumatic brain injury. J Trauma Acute Care Surg 85:873-880|
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