The absence of ADAMTS13 improves early outcomes in an experimental model of trauma with uncontrolled hemorrhage.

Abstract

Bleeding after trauma is aggravated by trauma-induced coagulopathy (TIC). In trauma patients with shock, ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) antigen is decreased, but its activity can be increased, possibly due to specific cleavage by plasmin. Increased ADAMTS13 activity could aggravate TIC and bleeding. Therefore, this study aimed to determine whether knocking-out ADAMTS13 is protective after trauma with uncontrolled bleeding. Furthermore, we examined the effect of plasmin inhibition with tranexamic acid (TXA) on ADAMTS13 antigen and activity. Wild-type and ADAMTS13 knockout (ADAMTS13 KO ) mice were anesthetized, mechanically ventilated, and subjected to traumatic injury with uncontrolled hemorrhage. In a separate experiment, wild-type mice underwent the same traumatic injury, but with additional blood withdrawal to induce shock and treatment with a single dose of TXA or vehicle. Outcomes included mortality, ADAMTS13 activity, von Willebrand factor (VWF) multimers, and rotational thromboelastometry (ROTEM). ADAMTS13 KO mice showed significantly lower mortality rates after trauma compared with wild-type mice (13% vs. 47%, P =0.046), with significantly higher VWF multimers. ROTEM parameters did not differ significantly between ADAMTS13 KO and wild-type mice. In the wild-type mice subjected to trauma and shock, there was a significant increase in ADAMTS13 activity, which correlated with shock severity. Treatment with TXA significantly reduced mortality, but had no significant effect on ADAMTS13 antigen or activity. Knocking-out ADAMTS13 is associated with improved early survival following trauma, demonstrating a role for ADAMTS13 in contributing to early TIC and bleeding. While ADAMTS13 activity increases after trauma and shock, its levels appear unaffected by TXA. ( J Trauma Acute Care Surg 2026;00:000-000 © 2026 The Author(s). Published by Wolters Kluwer Health, LLC. on behalf of the American Association for the Surgery of Trauma.). Level V.