Anti-high-mobility group box-1 treatment strategies improve trauma-induced coagulopathy in a mouse model of trauma and shock

Pieter H. Sloos, M. Adrie W. Maas, Joost C.M. Meijers, Rienk Nieuwland, Joris J.T.H. Roelofs, Nicole P. Juffermans, Derek J.B. Kleinveld*

*Corresponding author for this work

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Background: Trauma-induced coagulopathy is associated with platelet dysfunction and contributes to early mortality after traumatic injury. Plasma concentrations of the damage molecule high-mobility group box-1 (HMGB-1) increase after trauma, which may contribute to platelet dysfunction. We hypothesised that inhibition of HMGB-1 with a monoclonal antibody (mAb) or with recombinant thrombomodulin (rTM) improves trauma-induced coagulopathy in a murine model of trauma and shock. Methods: Male 129S2/SvPasOrlRJ mice were anaesthetised, mechanically ventilated, and randomised into five groups: (i) ventilation control (VENT), (ii) trauma/shock (TS), (iii) TS+anti-HMGB-1 mAb (TS+AB), (iv) TS+rTM (TS+TM), and (v) TS+anti-HMGB-1 mAb+rTM (TS+COMBI). Primary outcome was rotational thromboelastometry EXTEM. Secondary outcomes included tail bleeding time, platelet count, plasma HMGB-1 concentration, and platelet activation. Results: Trauma and shock resulted in a hypocoagulable thromboelastometry profile, increased plasma HMGB-1, and increased platelet activation markers. TS+AB was associated with improved clot firmness after 5 min compared with TS (34 [33–37] vs 32 [29–34] mm; P=0.043). TS+COMBI was associated with decreased clot formation time (98 [92–125] vs 122 [111–148] s; P=0.018) and increased alpha angle (77 [72–78] vs 69 [64–71] degrees; P=0.003) compared with TS. TS+COMBI also reduced tail bleeding time compared with TS (P=0.007). The TS+TM and TS+COMBI groups had higher platelet counts compared with TS (P=0.044 and P=0.041, respectively). Conclusions: Inhibition of HMGB-1 early after trauma in a mouse model improves clot formation and strength, preserves platelet count, and decreases bleeding time.

Original languageEnglish
Pages (from-to)687-697
Number of pages11
JournalBritish Journal of Anaesthesia
Issue number6
Early online date24 Mar 2023
Publication statusPublished - Jun 2023

Bibliographical note

Funding Information:
This study was funded by the European Society for Anesthesiology and Intensive Care (ESAIC) project grant 2021. Illustrations were created with BioRender ( ).

Publisher Copyright:
© 2023 The Authors


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