Model of thrombin generation in hemophilia. (A) Thrombin generation was modeled using the parameters of hockin.py modified to include rate constants and concentrations for inhibitors taken from Table 1. Plasma concentrations of factor VIII with 100% AT are indicated with “normal.” The shaded area encompasses the modeled range of thrombin generation values when the inhibitors are collectively set to the extremes of their reference ranges (AT, 86%-128%31; HC, 70%-130%32; A2M, 70%-155%33; and A1PI, 53%-133%34). In hemophilia A, the factor VIII concentration was set to 0. HC, A2M, and A1PI were set to the values shown in Table 1. AT was set to the indicated value. Modeled free thrombin is shown as a function of time. (B) The integrated thrombin was calculated from the free thrombin shown in panel A.
