Activation of innate immunity by bacterial products leads to Tlr4-MyD88–dependent inflammation and induction of the coagulation initiator TF. Coupling of Tlr4 to TRIF-IFN-α/βR1 targets nuclear localization sequences (NLS) of HMGB1 and increases availability of cytosolic HMGB1 for secretion and extracellular functions. In macrophages, LPS delivered by HMGB1 triggers activation of the noncanonical caspase 11 (Casp11) for gasdermin D (GSDMD) and transmembrane protein 16F (TMEM16F)-mediated PS translocation and TF-dependent DIC. TNFα, tumor necrosis factor α.