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Observational Study
. 2023 Dec 1;95(6):925-934.
doi: 10.1097/TA.0000000000004019. Epub 2023 Jul 5.

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

Julia R Coleman  1 , Angelo D'Alessandro, Ian LaCroix, Monika Dzieciatkowska, Patrick Lutz, Sanchayita Mitra, Fabia Gamboni, Wolram Ruf, Christopher C Silliman, Mitchell J Cohen
Affiliations
Observational Study

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

Julia R Coleman et al. J Trauma Acute Care Surg. .

Abstract

Background: The coagulopathy of traumatic brain injury (TBI) remains poorly understood. Contradictory descriptions highlight the distinction between systemic and local coagulation, with descriptions of systemic hypercoagulability despite intracranial hypocoagulopathy. This perplexing coagulation profile has been hypothesized to be due to tissue factor release. The objective of this study was to assess the coagulation profile of TBI patients undergoing neurosurgical procedures. We hypothesize that dura violation is associated with higher tissue factor and conversion to a hypercoagulable profile and unique metabolomic and proteomic phenotype.

Methods: This is a prospective, observational cohort study of all adult TBI patients at an urban, Level I trauma center who underwent a neurosurgical procedure from 2019 to 2021. Whole blood samples were collected before and then 1 hour following dura violation. Citrated rapid and tissue plasminogen activator (tPA) thrombelastography (TEG) were performed, in addition to measurement of tissue factory activity, metabolomics, and proteomics.

Results: Overall, 57 patients were included. The majority (61%) were male, the median age was 52 years, 70% presented after blunt trauma, and the median Glasgow Coma Score was 7. Compared with pre-dura violation, post-dura violation blood demonstrated systemic hypercoagulability, with a significant increase in clot strength (maximum amplitude of 74.4 mm vs. 63.5 mm; p < 0.0001) and a significant decrease in fibrinolysis (LY30 on tPAchallenged TEG of 1.4% vs. 2.6%; p = 0.04). There were no statistically significant differences in tissue factor. Metabolomics revealed notable increases in metabolites involved in late glycolysis, cysteine, and one-carbon metabolites, and metabolites involved in endothelial dysfunction/arginine metabolism/responses to hypoxia. Proteomics revealed notable increase in proteins related to platelet activation and fibrinolysis inhibition.

Conclusion: A systemic hypercoagulability is observed in TBI patients, characterized by increased clot strength and decreased fibrinolysis and a unique metabolomic and proteomics phenotype independent of tissue factor levels.

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Figures

Figure 1.
Figure 1.
Depiction of samples drawn pre- and post-dura violation (A), partial least square discriminant analysis (B), and hierarchical clustering map of the top 25 significant changes (C).
Figure 2.
Figure 2.
Top significant metabolites noted upon normalization of post-dura violation data to baseline values in volcano plot (A), with selected most significant changes (B).
Figure 3.
Figure 3.. Metabolome wide correlates to TEG MA, LY30, R parameters.
A) Raw metabolomics data was correlated with separate thrombelastography (TEG) parameters independently for ‘pre’ and ‘post’ time points using the Spearman method. Significant correlates (p-value < 0.05) are colored while insignificant hits remain grey. Coloring of significant hits were dictated by the respective TEG parameter as described in the legend. Blue corresponded to maximum amplitude (MA), gold corresponded to LY30 (fibrinolysis 30 minutes after MA), and orange corresponded to R (reaction time, time to clot formation). The correlation results from each time point were plotted together and differentiated by shape. Such that, ‘pre’ was represented with a triangle and ‘post’ was represented with a circle. B) Top correlates were selected for further analysis by linear regression. The line of best fit was colored by time point, teal for ‘pre’ and red for ‘post’.
Figure 4.
Figure 4.. Proteome wide correlates to TEG MA, LY30, R parameters.
A) Raw proteomics data was correlated with separate TEG parameters independently for ‘pre’ and ‘post’ time points using the Spearman method. Significant correlates (p-value < 0.05) are colored while insignificant hits remain grey. Coloring of significant hits were dictated by the respective thrombelastography (TEG) parameter as described in the legend. Blue corresponded to maximum amplitude (MA), gold corresponded to LY30 (fibrinolysis 30 minutes after MA), and orange corresponded to R (reaction time, time to clot formation). The correlation results from each time point were plotted together and differentiated by shape. Such that, ‘pre’ was represented with a triangle and ‘post’ was represented with a circle. B) Top correlates were selected for further analysis by linear regression. The line of best fit was colored by time point, teal for ‘pre’ and red for ‘post’.
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References

    1. Yang F, Peng C, Peng L, Wang J, Li Y, Li W. A Machine Learning Approach for the Prediction of Traumatic Brain Injury Induced Coagulopathy. Frontiers in Medicine. 2021;8:792689. - PMC - PubMed
    1. Hubbard WB, Dong JF, Cruz MA, Rumbaut RE. Links between thrombosis and inflammation in traumatic brain injury. Thrombosis Research. 2021;198:62–71. - PMC - PubMed
    1. Di Battista AP, Rizoli SB, Lejnieks B, Min A, Shiu MY, Peng HT, et al. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury. Shock. 2016;46(3 Suppl 1):96–103. - PMC - PubMed
    1. Lee TH, Hampton DA, Diggs BS, McCully SP, Kutcher M, Redick BJ, et al. Traumatic brain injury is not associated with coagulopathy out of proportion to injury in other body regions. The Journal of Trauma and Acute Care Surgery. 2014;77(1):67–72. - PubMed
    1. Abdelmalik PA, Boorman DW, Tracy J, Jallo J, Rincon F. Acute Traumatic Coagulopathy Accompanying Isolated Traumatic Brain Injury is Associated with Worse Long-Term Functional and Cognitive Outcomes. Neurocritical Care. 2016;24(3):361–70. - PubMed

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