Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial.
Journal
The journal of trauma and acute care surgery
ISSN: 2163-0763
Titre abrégé: J Trauma Acute Care Surg
Pays: United States
ID NLM: 101570622
Informations de publication
Date de publication:
01 11 2023
01 11 2023
Historique:
medline:
26
10
2023
pubmed:
1
5
2023
entrez:
1
5
2023
Statut:
ppublish
Résumé
In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days ( p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors ( p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors ( p = 0.03). Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. Therapeutic/Care Management; Level III.
Sections du résumé
BACKGROUND
In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial.
METHODS
We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors.
RESULTS
We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days ( p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors ( p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors ( p = 0.03).
CONCLUSION
Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion.
LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
Identifiants
pubmed: 37125811
doi: 10.1097/TA.0000000000003955
pii: 01586154-990000000-00349
pmc: PMC10615664
mid: NIHMS1895282
doi:
Substances chimiques
Tranexamic Acid
6T84R30KC1
Antifibrinolytic Agents
0
Syndecan-1
0
Banques de données
ClinicalTrials.gov
['NCT02086500']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
642-648Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM119526
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
Références
N Engl J Med. 2018 Jan 25;378(4):370-379
pubmed: 29365303
Cell Rep Med. 2021 Dec 21;2(12):100478
pubmed: 35028617
N Engl J Med. 2018 Jul 26;379(4):315-326
pubmed: 30044935
Shock. 2018 Apr;49(4):420-428
pubmed: 28945676
Ann Surg. 2022 Oct 1;276(4):673-683
pubmed: 35861072
J Trauma Acute Care Surg. 2022 May 1;92(5):812-820
pubmed: 35067525
PLoS One. 2017 Dec 19;12(12):e0189870
pubmed: 29261771
J Trauma Acute Care Surg. 2016 Aug;81(2):358-65
pubmed: 27027557
Chest. 2019 Mar;155(3):587-594
pubmed: 30392791
Cell Tissue Res. 2014 Mar;355(3):607-19
pubmed: 24435645
J Crit Care. 2014 Jun;29(3):327-33
pubmed: 24581948
JAMA Neurol. 2021 Mar 1;78(3):338-345
pubmed: 33284310
Trials. 2017 Jan 31;18(1):48
pubmed: 28143564
J Thromb Haemost. 2019 Jun;17(6):852-862
pubmed: 30985957
Crit Care. 2017 Feb 9;21(1):25
pubmed: 28179016
Ann Surg. 2021 Sep 1;274(3):419-426
pubmed: 34132695
Lancet. 2018 Jan 13;391(10116):97-98
pubmed: 29126598
Arch Surg. 2012 Feb;147(2):113-9
pubmed: 22006852
Ann Surg. 2017 Mar;265(3):597-603
pubmed: 27144442
J Head Trauma Rehabil. 2020 Sep/Oct;35(5):317-323
pubmed: 32881765
Ann Surg. 2007 May;245(5):812-8
pubmed: 17457176
JAMA Surg. 2020 Oct 05;:
pubmed: 33016996
Trauma Surg Acute Care Open. 2021 Mar 02;6(1):e000619
pubmed: 33748428
Nat Rev Dis Primers. 2021 Apr 29;7(1):30
pubmed: 33927200
JCI Insight. 2020 Apr 23;5(8):
pubmed: 32229722
JAMA Netw Open. 2020 Oct 1;3(10):e2016869
pubmed: 33057642
Lancet. 2019 Nov 9;394(10210):1713-1723
pubmed: 31623894
J Trauma Acute Care Surg. 2022 Jul 1;93(1):52-58
pubmed: 35393385
Health Technol Assess. 2013 Mar;17(10):1-79
pubmed: 23477634
J Trauma Acute Care Surg. 2017 Sep;83(3):398-405
pubmed: 28538641
J Trauma Acute Care Surg. 2020 Nov;89(5):908-914
pubmed: 32472902
Lancet. 2018 Jan 13;391(10116):125-132
pubmed: 29126600
Nat Immunol. 2018 Apr;19(4):327-341
pubmed: 29507356
Nat Commun. 2022 Nov 10;13(1):6789
pubmed: 36357394
Transfusion. 2022 Aug;62 Suppl 1:S301-S312
pubmed: 35834488
Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2514-23
pubmed: 17872453
J Am Coll Surg. 2018 Dec;227(6):587-595
pubmed: 30243993
Crit Care. 2022 Jan 30;26(1):33
pubmed: 35094711
J Trauma Acute Care Surg. 2017 Jun;82(6):1080-1086
pubmed: 28328682
Lancet. 2019 Nov 9;394(10210):1687-1688
pubmed: 31623893
J Trauma Acute Care Surg. 2018 Jan;84(1):75-80
pubmed: 29040203
J Thromb Haemost. 2015 Jun;13 Suppl 1:S195-9
pubmed: 26149023
JAMA Netw Open. 2022 Mar 01;5(3):e220625
pubmed: 35230436
J Crit Care. 2022 Jun;69:154010
pubmed: 35183892