• Pieter H Sloos, M Adrie W Maas, MeijersJoost C MJCMAmsterdam UMC Location University of Amsterdam, Department of Experimental Vascular Medicine, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, the Netherlands; Sanquin Rese, Rienk Nieuwland, RoelofsJoris J T HJJTHAmsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, the Netherlands., Nicole P Juffermans, and KleinveldDerek J BDJBAmsterdam UMC Location University of Amsterdam, Department of Intensive Care Medicine, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam.
• Amsterdam UMC Location University of Amsterdam, Department of Intensive Care Medicine, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam, the Netherlands.
• Br J Anaesth. 2023 Jun 1; 130 (6): 687697687-697.

BackgroundTrauma-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.MethodsMale 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.ResultsTrauma 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).ConclusionsInhibition of HMGB-1 early after trauma in a mouse model improves clot formation and strength, preserves platelet count, and decreases bleeding time.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

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