Thromboinflammatory activities of FXII in vivo. Contact system proteins FXII, HK, and PK assemble on cell surfaces. Contact with surface-exposed nonsoluble and plasma-borne soluble contact activators, including polyP or misfolded protein aggregates (PAgg) and heparin (Hep) or oversulfated chondroitin sulfate (OSCS), respectively, leads to the active protease FXIIa. FXIIa in turn triggers thrombosis via the FXI-mediated intrinsic coagulation pathway. FXIIa also activates PK that produces BK from HK. BK activates kinin B2 receptors (B2R), whereas the BK metabolite des-Arg9 BK binds to kinin B1 receptors (B1R), both of which drive inflammation. C1INH regulates FXIIa and PK enzymatic activity.