A broad overview of the components that are subject to inhibition under 3 sets of conditions (many of the coagulation steps are omitted). For an accurate analysis, see supplemental Figure 6 in the article by Zhu et al that begins on page 1494. Platelets adhere to collagen and are partially activated releasing polyphosphate from dense granules (dark spots on the platelets). During fibrin formation, fibrin structure is altered by association with polyphosphate, leading to a structure that is more resistant to lysis. (A) Factor XII is activated to factor XIIa. Factor XIIa activates factor XI to factor XIa, which activates factor IX to factor IXa, leading to thrombin (IIa) generation and fibrin formation. (B) Tissue factor initiates the generation of a small amount of thrombin (IIa) that binds to polyphosphate and activates factor XI to factor XIa. Additional factor XIa is generated from factor XIIa formed by contact activation. Factor XIa activates factor IX to factor IXa, leading to thrombin (IIa) generation and fibrin formation. (C) At high tissue factor, sufficient factor IX is activated to factor IXa to drive thrombin (IIa) generation and fibrin formation. polyP, polyphosphate; TF, tissue factor.