Andrew R Gosselin, Olivia Parker, Hajer Ali Sinan, Joseph S Hanna, Julie Goswami, Valerie Tutwiler
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引用次数: 0
Abstract
Background: Traumatic injury is a leading cause of death, in large part driven by coagulopathy-associated hemorrhage and thrombotic complications. Identification of biological pathways and therapeutic targets has been limited. We performed a proteomic analysis using plasma isolated from trauma patients and assessed the proteome relation to clot formation and stability.
Methods: Platelet-poor plasma was isolated from trauma patients upon emergency department arrival. Coagulation was characterized using rheology, turbidity, and confocal microscopy. Proteomics were measured using liquid chromatography-mass spectrometry and compared between: 1) healthy donors vs . trauma patients, 2) nonsevere vs . severe injury, 3) survived vs . deceased patients, 4) penetrating vs . blunt injuries, 5) traumatic brain injury (TBI) vs . no-TBI, and 6) presence vs . absence of physiological shock. Spearman correlations were calculated between coagulation tests, clinical vitals, and proteomics data. Gene ontology and Search Tool for the Retrieval of Interacting Genes/Proteins analysis identified enrichment of biological processes and interconnectedness of mortality-related proteins.
Results: Hemostatic processes were enriched in healthy donors, severe injury patients, surviving patients, no-TBI patients, and patients not exhibiting shock. Plasminogen activator inhibitor 3 was in higher abundance in those who survived their injuries compared with those who died. Plasminogen activator inhibitor 3 was correlated with faster clotting time, thrombin generation, and decreased D-dimer. Proteins higher in deceased patients compared with those who survived, such as prostaglandin-H2 isomerase, related to immune activity, correlated with weaker clots and increased D-dimer.
Conclusions: This exploratory analysis of plasma proteomics in trauma patients identified potential markers related to coagulation and immune activity, which may contribute to coagulopathy-associated mortality after injury and serve as therapeutic targets.
期刊介绍：
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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