Figure 3. Threshold response to TF surface concentration and injury size.
Experiments and simulations show that TF surface concentration or injury size must exceed a threshold value to yield a burst in thrombin generation characteristic of the propagation phase of coagulation. A. A computational models of thrombus formation under flow predict a threshold response in thrombin generation to surface TF concentrations that is a function of wall shear rate (100, 500, 1500 s−1). Note that above ~15 fmol/cm2 of TF that thrombin generation saturates suggesting reaction-limited behavior. B. Under static conditions, a threshold TF spots size is necessary to initiate coagulation from plasma.48 Below the threshold size coagulation products diffuse away from the spot before they can initiate robust thrombin generation. C. A computational model of plasma flowing over TF spots separated by TM coated walls. At low TM surface concentrations (top panel), thrombin generation is additive between adjacent TF sites because there is not enough APC to quench coagulation products between site. At high TM concentrations (bottom panel), the interaction between sites can be repressed.51