Overview of coagulation system. Coagulation is initiated by the extrinsic pathway when tissue factor (TF) exposed at sites of vascular injury binds and activates FVII. The activated FVII (FVIIa)–TF complex activates FX in the common pathway to generate prothrombinase, which generates thrombin. Additional activation of coagulation occurs when thrombin-activated platelets release polyphosphate (poly-P) and activated neutrophils extrude DNA and RNA to form NETs. NETs and poly-P activate the contact pathway, which yields FXIa and leads to additional thrombin generation via the common pathway. Poly-P amplifies this pathway by promoting thrombin-mediated activation of FXI.