Provisional Patent Application: Hybrid System Modeling of Human Blood Clotting

The process of blood coagulation in mammals is complicated, and involves the interaction of more than a dozen coagulation factors as well as a number of proteins from the kinin-kallikrein system and protein inhibitors. Attempts to model coagulation mathematically have previously focused on a smaller subset of interactions, perhaps one of the pathways or just a portion of one of them (cf. [1],[2], [3],[4],[5], [6] and [7]) using continuous-time chemical rate di erential equations. There are, however, at least two reasons why this methodology is inadequate for modeling the entire coagulation cascade. First, there is reason to believe [8] that certain events in the cascade are better modeled by punctuated phase changes, rather than as evolving continuously. For example, antithrombin III and a_{2-macroglobulin are only able to inhibit thrombin activation below a certain threshold of thrombin [9]. Similarly, concentrations of free zinc ions are thought to toggle the activation of several of the proteins of the contact activation portion of the clotting cascade [10],[11]. Second, the problem with modeling coagulation as a purely continuous-time phenomenon is that the process is too complicated (with thresholds and discontinous phase changes) to permit a precise description of the various parameters and their interactions in terms of di erential equations. Our invention is a novel modeling framework and software program which constructs a robust, faithful, interactive, and graphical computer simulation of the entire coagulation process. The framework is faithful in that it accurately models mammalian blood clotting; robust in the sense of doing so over a wide range of parameter settings; interactive in that the system operation and parameter settings can be interactively changed while the software program is executing, and hypothetical "what-if" simulations performed; and graphical in that the model is a formal graphical structure that supports visualization of the clotting process as well as exact quantitative analysis. Technically, the invention uses an emerging alternative modeling paradigm in which the coagulation cascade is viewed as a "hybrid}