Impact of hemostatic plug size on thrombin and APC concentration. (A) Reaction surface distribution. PC is converted to APC on all surfaces lining the vessel lumen (bold black lines). Thrombin generation occurs on surfaces of the extravascular compartment and the injury site walls, with or without intravascular surfaces that are protected by the hemostatic plug (bold red lines): default plug size with intravascular thrombin generation (i), default plug size without intravascular thrombin generation (ii), and small plug size without intravascular thrombin generation (iii). (B) Thrombin concentration fields for each of the geometries described in panel A. When the intravascular thrombin generation surfaces are removed without changing the shape or size of the hemostatic plug, the resulting thrombin concentration field remains virtually unchanged (i vs ii). This occurs because the thrombin generated on the injury walls and extravascular space can backpropagate in the lumen sheltered by the hemostatic plug via diffusion. (C) APC concentration fields for each of the geometries described in panel A. Note the reduction in APC concentration when reaction surfaces capable of generating APC become unsheltered from flow (iii).