HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma

Abstract Massive bleeding causes approximately 50% of deaths in patients with major trauma. Most patients die within 6 h of injury, which is preventable in at least 10% of cases. For these patients, early activation of the massive transfusion protocol (MTP) is a critical survival factor. With severe...

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Main Authors: Michal Frelich, Marek Bebej, Jan Pavlíček, Filip Burša, Vojtěch Vodička, Zdeněk Švagera, Adéla Kondé, Ondřej Jor, Markéta Bílená, Tereza Romanová, Peter Sklienka
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Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-89139-1
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author Michal Frelich
Marek Bebej
Jan Pavlíček
Filip Burša
Vojtěch Vodička
Zdeněk Švagera
Adéla Kondé
Ondřej Jor
Markéta Bílená
Tereza Romanová
Peter Sklienka
author_facet Michal Frelich
Marek Bebej
Jan Pavlíček
Filip Burša
Vojtěch Vodička
Zdeněk Švagera
Adéla Kondé
Ondřej Jor
Markéta Bílená
Tereza Romanová
Peter Sklienka
author_sort Michal Frelich
collection DOAJ
description Abstract Massive bleeding causes approximately 50% of deaths in patients with major trauma. Most patients die within 6 h of injury, which is preventable in at least 10% of cases. For these patients, early activation of the massive transfusion protocol (MTP) is a critical survival factor. With severe trauma, high-mobility group box 1 (HMGB-1, i.e., amphoterin) is released into the blood, and its levels correlate with the development of a systemic inflammatory response, traumatic coagulopathy, and fibrinolysis. Previous work has shown that higher levels of HMGB-1 are associated with a higher use of red blood cell transfusions. We conducted a retrospective analysis of previous prospective single-center study to assess the value of admission HMGB-1 levels in predicting activation of MTP in the emergency department. From July 11, 2019, to April 23, 2022, a total of 104 consecutive adult patients with severe trauma (injury severity score > 16) were enrolled. A blood sample was taken at admission, and HMGB-1 was measured. MTP activation in the emergency department was recorded in the study documentation. The total amount of blood products and fibrinogen administered to patients within 6 h of admission was monitored. Among those patients with massive bleeding requiring MTP activation, we found significantly higher levels of HMGB-1 compared to patients without MTP activation (median [interquartile range]: 84.3 µg/L [34.2–145.9] vs. 21.1 µg/L [15.7–30.4]; p < 0.001). HMGB-1 level showed good performance in predicting MTP activation, with an area under the receiver operating characteristic curve of 0.84 (95% CI 0.75–0.93) and a cut-off value of 30.55 µg/L. HMGB-1 levels correlated significantly with the number of red blood cell units (rs [95% CI] 0.46 [0.28–0.61]; p < 0.001), units of fresh frozen plasma (rs 0.46 [0.27–0.61]; p < 0.001), platelets (rs 0.48 [0.30–0.62]; p < 0.001), and fibrinogen (rs 0.48 [0.32–0.62]; p < 0.001) administered in the first 6 h after hospital admission. Admission HMGB-1 levels reliably predict severe bleeding requiring MTP activation in the emergency department and correlate with the amount of blood products and fibrinogen administered during the first 6 h of hemorrhagic shock resuscitation. Trial registration: NCT03986736. Registration date: June 4, 2019.
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spelling doaj-art-ba814e2a45fc4f6eb1e27806617fe0272025-02-09T12:29:22ZengNature PortfolioScientific Reports2045-23222025-02-0115111210.1038/s41598-025-89139-1HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe traumaMichal Frelich0Marek Bebej1Jan Pavlíček2Filip Burša3Vojtěch Vodička4Zdeněk Švagera5Adéla Kondé6Ondřej Jor7Markéta Bílená8Tereza Romanová9Peter Sklienka10Department of Anaesthesiology and Intensive Care Medicine, University Hospital OstravaDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital OstravaDepartment of Pediatrics, Faculty of Medicine, University Hospital Ostrava, Ostrava UniversityDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital OstravaDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital OstravaInstitute of Laboratory Diagnostics, University Hospital OstravaDepartment of Applied Mathematics, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of OstravaDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital OstravaDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital OstravaDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital OstravaDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital OstravaAbstract Massive bleeding causes approximately 50% of deaths in patients with major trauma. Most patients die within 6 h of injury, which is preventable in at least 10% of cases. For these patients, early activation of the massive transfusion protocol (MTP) is a critical survival factor. With severe trauma, high-mobility group box 1 (HMGB-1, i.e., amphoterin) is released into the blood, and its levels correlate with the development of a systemic inflammatory response, traumatic coagulopathy, and fibrinolysis. Previous work has shown that higher levels of HMGB-1 are associated with a higher use of red blood cell transfusions. We conducted a retrospective analysis of previous prospective single-center study to assess the value of admission HMGB-1 levels in predicting activation of MTP in the emergency department. From July 11, 2019, to April 23, 2022, a total of 104 consecutive adult patients with severe trauma (injury severity score > 16) were enrolled. A blood sample was taken at admission, and HMGB-1 was measured. MTP activation in the emergency department was recorded in the study documentation. The total amount of blood products and fibrinogen administered to patients within 6 h of admission was monitored. Among those patients with massive bleeding requiring MTP activation, we found significantly higher levels of HMGB-1 compared to patients without MTP activation (median [interquartile range]: 84.3 µg/L [34.2–145.9] vs. 21.1 µg/L [15.7–30.4]; p < 0.001). HMGB-1 level showed good performance in predicting MTP activation, with an area under the receiver operating characteristic curve of 0.84 (95% CI 0.75–0.93) and a cut-off value of 30.55 µg/L. HMGB-1 levels correlated significantly with the number of red blood cell units (rs [95% CI] 0.46 [0.28–0.61]; p < 0.001), units of fresh frozen plasma (rs 0.46 [0.27–0.61]; p < 0.001), platelets (rs 0.48 [0.30–0.62]; p < 0.001), and fibrinogen (rs 0.48 [0.32–0.62]; p < 0.001) administered in the first 6 h after hospital admission. Admission HMGB-1 levels reliably predict severe bleeding requiring MTP activation in the emergency department and correlate with the amount of blood products and fibrinogen administered during the first 6 h of hemorrhagic shock resuscitation. Trial registration: NCT03986736. Registration date: June 4, 2019.https://doi.org/10.1038/s41598-025-89139-1Major traumaBleedingMassive transfusion protocolHMGB-1
spellingShingle Michal Frelich
Marek Bebej
Jan Pavlíček
Filip Burša
Vojtěch Vodička
Zdeněk Švagera
Adéla Kondé
Ondřej Jor
Markéta Bílená
Tereza Romanová
Peter Sklienka
HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma
Scientific Reports
Major trauma
Bleeding
Massive transfusion protocol
HMGB-1
title HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma
title_full HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma
title_fullStr HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma
title_full_unstemmed HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma
title_short HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma
title_sort hmgb 1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma
topic Major trauma
Bleeding
Massive transfusion protocol
HMGB-1
url https://doi.org/10.1038/s41598-025-89139-1
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