Activated neutrophils release NETs, which are scaffolds of decondensated DNA and histones. Noubouossie et al report that individual NET components such as free DNA and histone proteins promote thrombin generation (TG) through the following 3 pathways: (1) activation of the contact pathway via factor XII, (2) amplification of tissue factor (TF)–dependent TG, (3) and activation of platelets via histones H3 and H4. (4) In addition, natural anticoagulants such as tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) can be inactivated by myeloperoxidase (MPO) and serine proteases (ie, neutrophil elastase [NE]). Professional illustration by Patrick Lane, ScEYEnce Studios.