Figure 5.

Spatial TF distribution defines the role of positive feedback for fVII activation in clotting. To compare the roles of fV and fVII feedback loops, initiation time dependencies on TF concentration and density were calculated for normal plasma and plasma without either fVII or fV activation. A detailed, mechanism-driven mathematical model was used. (Left) When TF was distributed homogeneously, only the fV activation feedback loop was essential for clotting. (Middle) When immobilized TF was uniformly distributed over the surface in 3D computer simulations, the feedback loops for both fV and fVII activation influenced the initiation time. (Right) TF was uniformly immobilized at the surface, and the fXa diffusion coefficient was increased by 10⁴ to mimic homogeneous TF distribution. The role of positive feedback in the fVII activation of clotting disappeared, suggesting that fVII activation by fXa is important for the clotting process only when fXa is removed by diffusion; thus, additional fVIIa activated fXa and compensated for its diffusion.