Schematic overview of receptor and cofactor interactions of the contact factors for thrombotic (top) and inflammatory (bottom) pathways. Assembly of the contact system via gC1q-R (with elevated Zn2+) generates PKa, FXIIa, and BK is produced on the surface of endothelial cells (bottom). Also shown is the FXII and HK interactions with the uPAR receptor and CK1. FXIIa activates plasma coagulation cascades via FXI on the surface of platelets (top). The platelet GP1b-IX receptor GP1bα chain interaction with FXI–HK and PKa binding to the activated platelet integrin αIIbβ3 is also depicted. Neutrophils are also depicted releasing NETs known to associate with contact proteins. Abbreviations: FXII, factor XII; FXIIa, activated FXII; PK, prekallikrein; PKa, activated PK; FXI, factor XI; FXIa, activated FXI; HK, high molecular-weight kininogen; BK, bradykinin; uPAR, urokinase receptor; GPIbα, platelet glycoprotein Ib; CK1, cytokeratin 1; gC1q-R, receptor for complement protein C1q; Mac-1, macrophage-1 antigen receptor; PolyP, polyphosphate; RBC, red blood cells; NETs, neutrophil extracellular traps.