Fig 4. Sensitivity of total thrombin generation to plasma levels.
Variation in the A,D) lag time; B,E) maximum relative rate; C,F) final concentration; to zymogen and chemical inhibitor levels using the local (OAT) method (A-C) and global Sobol method (D-F). Local: Sensitivities that lie between 0.75 and 1 (blue), between 0.25 and 0.75 (magenta), less than 0.25 (cyan) determine the rank-ordered list of initial levels. The percent change of thrombin generation measures from baseline model output for each initial condition are represented by triangles. The direction of variation of the input parameter is indicated with an upwards or downwards facing triangle. Global: First and Total Order Sobol indices are plotted as bars with errors of 2 standard deviation about the mean, computed with 5,000 bootstrap samples of the original 110,000 function evaluations. The coefficient of variation is included to provide a scale for the fraction of variance. No total order index was statistically significantly larger than the first order index, indicating that the model output is not significantly effected by interactions between the parameters considered here.