A metabolomic and proteomic analysis of pathologic hypercoagulability in traumatic brain injury patients after dura violation

Coleman, Julia R.; D’Alessandro, Angelo; LaCroix, Ian S; Dzieciątkowska, Monika; Lutz, Patrick; Mitra, Sanchayita; Gamboni, Fabia; Ruf, Wolfram; Silliman, Christopher C.; Cohen, Mitchell J.

doi:10.1097/ta.0000000000004019

Cited by 3 publications

(2 citation statements)

References 49 publications

(101 reference statements)

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“…Alterations to this pathway in critically injured patients receiving transfusion are observed upon intravascular hemolysis of transfused RBCs, or in sickle cell patients where basal levels of hemolysis are pathologically high . Of note, dysregulation of this pathway in the context of sickle cell disease has been associated with vaso-occlusive crisis as a function of hypercoagulable blood, a combination of metabolic and clotting phenotypes that we have recently reported in the context of TBI with dura violation . Zone-I increased plasma levels of urea cycle intermediates and polyamine spermidine.…”

Section: Discussionmentioning

confidence: 58%

“…34 Of note, dysregulation of this pathway in the context of sickle cell disease has been associated with vaso-occlusive crisis as a function of hypercoagulable blood, a combination of metabolic and clotting phenotypes that we have recently reported in the context of TBI with dura violation. 35 Zone-I increased plasma levels of urea cycle intermediates and polyamine spermidine. Since the urea cycle occurs intracellularly in mitochondria, detection of urea cycle intermediates within plasma indicates occurrence of metabolite transport or release through cell damage, cell lysis, or vesiculation.…”

Section: ■ Discussionmentioning

confidence: 99%

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Multiomics Signatures of Coagulopathy in a Polytrauma Swine Model Contrasted with Severe Multisystem Injured Patients

LaCroix,

Moore,

Cralley

et al. 2024

J. Proteome Res.

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Trauma-induced coagulopathy (TIC) is a leading contributor to preventable mortality in severely injured patients. Understanding the molecular drivers of TIC is an essential step in identifying novel therapeutics to reduce morbidity and mortality. This study investigated multiomics and viscoelastic responses to polytrauma using our novel swine model and compared these findings with severely injured patients. Molecular signatures of TIC were significantly associated with perturbed coagulation and inflammation systems as well as extensive hemolysis. These results were consistent with patterns observed in trauma patients who had multisystem injuries. Here, intervention using resuscitative endovascular balloon occlusion of the aorta following polytrauma in our swine model revealed distinct multiomics alterations as a function of placement location. Aortic balloon placement in zone-1 worsened ischemic damage and mitochondrial dysfunction, patterns that continued throughout the monitored time course. While placement in zone-III showed a beneficial effect on TIC, it showed an improvement in effective coagulation. Taken together, this study highlights the translational relevance of our polytrauma swine model for investigating therapeutic interventions to correct TIC in patients.

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Section: Discussionmentioning

confidence: 58%

Section: ■ Discussionmentioning

confidence: 99%

Multiomics Signatures of Coagulopathy in a Polytrauma Swine Model Contrasted with Severe Multisystem Injured Patients

LaCroix,

Moore,

Cralley

et al. 2024

J. Proteome Res.

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Omics markers of platelet transfusion in trauma patients

et al. 2023

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BackgroundEven in the era of the COVID‐19 pandemic, trauma remains the global leading cause of mortality under the age of 49. Trauma‐induced coagulopathy is a leading driver of early mortality in critically ill patients, and transfusion of platelet products is a life‐saving intervention to restore hemostasis in the bleeding patient. However, despite extensive functional studies based on viscoelastic assays, limited information is available about the impact of platelet transfusion on the circulating molecular signatures in trauma patients receiving platelet transfusion.Materials and MethodsTo bridge this gap, we leveraged metabolomics and proteomics approaches to characterize longitudinal plasma samples (n = 118; up to 11 time points; total samples: 759) from trauma patients enrolled in the Control Of Major Bleeding After Trauma (COMBAT) study. Samples were collected in the field, in the emergency department (ED), and at intervals up to 168 h (7 days) post‐hospitalization. Transfusion of platelet (PLT) products was performed (n = 30; total samples: 250) in the ED through 24 h post‐hospitalization. Longitudinal plasma samples were subjected to mass spectrometry‐based metabolomics and proteomics workflows. Multivariate analyses were performed to determine omics markers of transfusion of one, two, three, or more PLT transfusions.ResultsHigher levels of tranexamic acid (TXA), inflammatory proteins, carnitines, and polyamines were detected in patients requiring PLT transfusion. Correlation of PLT units with omics data suggested sicker patients required more units and partially overlap with the population requiring transfusion of packed red blood cell products. Furthermore, platelet activation was likely increased in the most severely injured patients. Fatty acid levels were significantly lower in PLT transfusion recipients (at time of maximal transfusion: Hour 4) compared with non‐recipients, while carnitine levels were significantly higher. Fatty acid levels restore later in the time course (e.g., post‐PLT transfusion).DiscussionThe present study provides the first multi‐omics characterization of platelet transfusion efficacy in a clinically relevant cohort of trauma patients. Physiological alterations following transfusion were detected, highlighting the efficacy of mass spectrometry‐based omics techniques to improve personalized transfusion medicine. More specialized clinical research studies focused on PLT transfusion, including organized pre and post transfusion sample collection and limitation to PLT products only, are required to fully understand subsequent metabolomic and proteomic alterations.

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The importance of the gut microbiome and its signals for a healthy nervous system and the multifaceted mechanisms of neuropsychiatric disorders

Riehl,

Fürst,

Kress

et al. 2024

Front. Neurosci.

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Increasing evidence links the gut microbiome and the nervous system in health and disease. This narrative review discusses current views on the interaction between the gut microbiota, the intestinal epithelium, and the brain, and provides an overview of the communication routes and signals of the bidirectional interactions between gut microbiota and the brain, including circulatory, immunological, neuroanatomical, and neuroendocrine pathways. Similarities and differences in healthy gut microbiota in humans and mice exist that are relevant for the translational gap between non-human model systems and patients. There is an increasing spectrum of metabolites and neurotransmitters that are released and/or modulated by the gut microbiota in both homeostatic and pathological conditions. Dysbiotic disruptions occur as consequences of critical illnesses such as cancer, cardiovascular and chronic kidney disease but also neurological, mental, and pain disorders, as well as ischemic and traumatic brain injury. Changes in the gut microbiota (dysbiosis) and a concomitant imbalance in the release of mediators may be cause or consequence of diseases of the central nervous system and are increasingly emerging as critical links to the disruption of healthy physiological function, alterations in nutrition intake, exposure to hypoxic conditions and others, observed in brain disorders. Despite the generally accepted importance of the gut microbiome, the bidirectional communication routes between brain and gut are not fully understood. Elucidating these routes and signaling pathways in more detail offers novel mechanistic insight into the pathophysiology and multifaceted aspects of brain disorders.

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A metabolomic and proteomic analysis of pathologic hypercoagulability in traumatic brain injury patients after dura violation

Cited by 3 publications

References 49 publications

Multiomics Signatures of Coagulopathy in a Polytrauma Swine Model Contrasted with Severe Multisystem Injured Patients

Multiomics Signatures of Coagulopathy in a Polytrauma Swine Model Contrasted with Severe Multisystem Injured Patients

Omics markers of platelet transfusion in trauma patients

The importance of the gut microbiome and its signals for a healthy nervous system and the multifaceted mechanisms of neuropsychiatric disorders

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