Indeed, neutrophil elastase associated with NETs degrades the anticoagulant protein, TFPI, thereby enhancing TF activity and thrombin generation.96 Histones activate platelets via TLR-2 and TLR-4 and enhance fibrin formation, while the contact activation system, via FXII activation, is initiated by negatively charged DNA.96,99 The activation of FXII not only initiates coagulation but also has important proinflammatory properties by way of its ability to liberate the generation of bradykinin, upregulate neutrophil function, and the generation of monocyte-derived proinflammatory cytokines.100