Analysis and Characterization of Trauma-Induced Coagulopathy

总体而言： 失控出血是暴露在严重创伤中的成年人死亡的主要原因。创伤致伤 凝血障碍(TIC)发生在损伤和休克之后，伴随着炎症和凝血的“风暴” 导致止血过程丧失能力的事件。抽搐会影响止血系统，因为 在系统的基础上发生的失调的过程，其中蛋白质分解系统破坏必要的 凝血成分。以前的研究已经发现，活化的蛋白C介导的破坏 辅因子Va和牵连的全身性纤溶活性，其中无调控的蛋白分解破坏 纤维蛋白原和部分血浆凝固系统。静脉采血中观察到的这些终末事件 抽动症患者是由体内过程引起的，涉及血液和血管中的蛋白质、细胞和细胞因子 进入血液的组织和组织损伤物质。TIC的原因和广度尚不清楚。 这一策略项目提供了对血浆蛋白、血细胞、 将血管内皮、血管和血管外组织转化为TIC，利用独特的 基础设施，包括已经资助的国防部参与创伤试验和系统生物学的地点。一个 凝血和炎症研究领域领先研究人员的全面团队方法 使用体外和体内方法的组合来确定对TLC负有责任的候选人的问题。 早期将实验室结果转化为有用的技术将通过一套5种战术创伤来实现 中锋。在这些研究的同时，与参与国防部临床试验的临床中心的互动将是 每个中心的研究人员将负责护理点研究和 血样的处理。收集技术将利用抑制性鸡尾酒来阻止体外，后 静脉切割术文物。血液/血浆样本将被运往安全的储存库，并使用新的 用于识别TIC事件自然历史的技术。战略研究项目的延续将是 取决于它们对创伤患者的诊断和治疗选择的潜在效用。 凝血、炎症和协调中心的摘要保持不变 呈件。

OVERALL: 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. TIC compromises 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 TIC are not understood. This TACTIC project 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 TlC. 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. Summaries for the Coagulation, Inflammation and Coordinating Center remain unchanged from the original submission.