Analysis and Characterization of Trauma-Induced Coagulopathy

创伤性凝血病的分析和表征

• 批准号: 9986376
• 负责人: James H. Morrissey
• 金额: $ 177.78万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9986376
• 关键词: Address; Adult; Animal Model; Basic Science; Blood; Blood Cells; Blood Coagulation Disorders; Blood Vessels; Blood specimen; Cause of Death; Cells; Clinical; Clinical Data; Clinical Research; Clinical Trials; Coagulation Process; Collection; Complex; Cultured Cells; Department of Defense; Diagnosis; Ensure; Evaluation; Event; Exposure to; Factor Va; Fibrinogen; Funding; Goals; Hemorrhage; Hemostatic Agents; Hormones; Immune response; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Infrastructure; Injury; Laboratories; Lead; Lipids; Logistics; Mediating; Mediator of activation protein; Methods; Molecular; Morbidity - disease rate; Morphologic artifacts; Natural History; Patients; Peptide Hydrolases; Plasma; Plasma Proteins; Process; Productivity; Proteins; Proteolysis; Research; Research Personnel; Research Project Grants; Resource Allocation; Sampling; Secure; Selection for Treatments; Ships; Shock; Site; Syndrome; System; Systems Biology; Techniques; Technology; Therapeutic Intervention; Tissues; Translating; Translational Research; Translations; Trauma; Trauma patient; Traumatic injury; Vascular Endothelium; Venous blood sampling; activated Protein C; biobank; cell injury; clinically relevant; cofactor; cytokine; exhaust; experience; improved; in vivo; member; mortality; multidisciplinary; new technology; novel; point of care; prevent; programs; repository; resource guides; trauma centers

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.

总体： 不受控制的出血是暴露于严重创伤的成人死亡的主要原因。创伤引起 凝血病（TIC）发生在损伤和休克后，伴随着炎症和凝血的“风暴 导致止血过程丧失能力的事件。TIC会损害止血系统， 在系统基础上发生的失调过程中，蛋白水解系统破坏了 凝血成分以前的研究已经确定了活化蛋白C介导的破坏， 辅因子Va和牵连的全身纤维蛋白溶解活性，其中不受调节的蛋白水解破坏 纤维蛋白原和血浆凝固系统的部分。这些终末事件在静脉采血中观察到， TIC患者是由涉及血液和血管中的蛋白质、细胞和细胞因子的体内过程引起的， 组织和组织损伤物质进入血液。TIC的原因和广度尚不清楚。 这个TACTIC项目提供了一个全面的评估血浆蛋白，血细胞， 血管内皮、血管和血管外组织对TIC的作用，利用独特的 基础设施，包括已经资助的涉及创伤试验和系统生物学的国防部网站。一 凝血和炎症研究领域的领先研究者采用的综合团队方法， 使用体外和体内方法的复合物来鉴定负责TlC的候选物的问题。 通过一组5个TACTIC创伤， 中心.在进行这些研究的同时，将与从事国防部临床试验的临床中心进行互动， 制定了每个中心的研究人员将负责床旁研究的计划， 血液样本的处理。收集技术将利用抑制性鸡尾酒来阻断离体、后 静脉切开术伪影血液/血浆样本将被运送到安全的储存库，并使用新的 技术来识别TIC事件的自然历史。TACTIC研究项目的继续将是 这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、炎症和协调中心的总结与原始版本保持不变 成绩.

项目成果

Reduced cleavage of von willebrand factor by ADAMTS13 is associated with microangiopathic acute kidney injury following trauma.

• DOI: 10.1097/mbc.0000000000001089
• 发表时间: 2022-01-01
• 期刊: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
• 作者: Plautz WE;Haldeman SH;Dyer MR;Sperry JL;Guyette FX;Loughran PA;Alvikas J;Hassoune A;Hoteit L;Alsaadi N;Zuckerbraun BS;Rollins-Raval MA;Raval JS;Mota RI;Neal MD;A TACTIC Publication
• 通讯作者: A TACTIC Publication

Astrocytes and pericytes attenuate severely injured patient plasma mediated expression of tight junction proteins in endothelial cells.

• DOI: 10.1371/journal.pone.0270817
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7

Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19.

• DOI: 10.1111/jth.15455
• 发表时间: 2021-09
• 期刊: Journal of thrombosis and haemostasis : JTH
• 作者: Hollerbach A;Müller-Calleja N;Pedrosa D;Canisius A;Sprinzl MF;Falter T;Rossmann H;Bodenstein M;Werner C;Sagoschen I;Münzel T;Schreiner O;Sivanathan V;Reuter M;Niermann J;Galle PR;Teyton L;Ruf W;Lackner KJ
• 通讯作者: Lackner KJ

Analysis of factor XIa, factor IXa and tissue factor activity in burn patients.

烧伤患者因子XIa、因子IXa及组织因子活性分析

• DOI: 10.1016/j.burns.2017.08.003
• 发表时间: 2018
• 期刊: Burns : journal of the International Society for Burn Injuries
• 作者: Shupp,JeffreyW;Prior,ShannonM;Jo,DanielY;Moffatt,LaurenT;Mann,KennethG;Butenas,Saulius
• 通讯作者: Butenas,Saulius

Packed Red Blood Cells Accumulate Oxidative Stress With Increased Storage Duration.

随着储存时间的增加，浓缩红细胞会积累氧化应激。

• DOI: 10.1097/shk.0000000000000828
• 发表时间: 2017
• 期刊: Shock (Augusta, Ga.)
• 作者: Preston,Kelsey;Harm,Sarah;Dreyfus,Nathan;Villalba,Nuria;Freeman,Kalev
• 通讯作者: Freeman,Kalev