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Endotheliopathy is Associated with a 24-hour Fibrinolysis Phenotype Described by Low TEG Lysis and High D-Dimer after Trauma: a Secondary Analysis of the PROPPR Study

Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA. University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama, USA. University of Alabama at Birmingham, School of Public Health, Birmingham, Alabama, USA. Center for Injury Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. Division of Acute Care Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA. Division of Acute Care Surgery, Department of Surgery, University of Texas Health Science Center at Houston, Houston, Texas, USA. Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, Texas, USA.

Annals of surgery open : perspectives of surgical history, education, and clinical approaches. 2022;3(1)
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Abstract
OBJECTIVES Determine associations between biomarkers of endotheliopathy, 24-hour fibrinolysis phenotypes and clinical outcomes after trauma. BACKGROUND The vascular endothelium is a critical regulator of hemostasis and organ function. The relationship between markers of endotheliopathy and fibrinolysis following trauma has not been evaluated. METHODS We performed a secondary analysis of prospectively collected biomarker data in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized controlled trial. We stratified subjects by 24-hour thromboelastography (TEG) percent clot lysis (LY30) and plasma D-dimer (DD) levels and evaluated differences in endotheliopathy biomarkers and clinical outcomes between subjects with one of four 24-hour fibrinolysis phenotypes: LY30 0.9-2.9% (LY30(norm)), LY30 >2.9% (LY30(high)), LY30 <0.9% and low DD (LY30(low)+DD(low)), and LY30 <0.9% and high DD (LY30(low)+DD(high)). RESULTS The analysis included 168 subjects with LY30(norm), 32 with LY30(high), 147 with LY30(low)+DD(low) and 124 with LY30(low)+DD(high). LY30(low)+DD(high) subjects had greater injury severity and a higher incidence of severe head injury, multiorgan failure (MOF), and mortality than the other phenotypes. All endotheliopathy biomarkers were significantly higher in the LY30(low)+DD(high) phenotype. Adjusting for injury severity, mechanism and head trauma, 24-hour angiopoietin-2 and soluble thrombomodulin were independently associated with the LY30(low)+DD(high) phenotype. Both endothelial biomarkers were discriminating for MOF. Subjects with thrombomodulin level >9.5 ng/mL and angiopoietin-2 level >3.6 ng/mL accounted for 64% of subjects who developed MOF. CONCLUSIONS In a multicenter trauma cohort, subjects with a fibrinolysis phenotype characterized by low TEG lysis and elevated DD 24 hours after injury have significantly worse endotheliopathy and clinical outcomes. Our findings support mechanistic evaluations of the role of the endothelium in fibrinolysis dysregulation that may drive late-stage organ injury.
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Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine