Leukocyte inflammation contributes to the pathophysiology of acute trauma-induced coagulopathy by oxidation and proteolysis of fibrinogen. In both in vitro and in vivo models of trauma, leukocytes generated mitochondrial superoxide, causing oxidation of the Aα and Bβ chains of fibrinogen and partial degradation of the Aα chains, leading to abnormal clot structure. Antioxidants suppressing mitochondrial superoxide reduced inflammation and oxidative stress and protected fibrinogen, preserving fibrin clot structure. Professional illustration by Patrick Lane, ScEYEnce Studios.