(620g) An Engineering Control System Paradigm for Quantitative Understanding of Hemostasis: A Mathematical Model of the Primary Hemostasis Actuator

Hemostasis, the physiological process that arrests bleeding and keeps blood within the blood vessel, consists of a set of reactions that can be divided into various functional components. Normal functioning of the components is necessary to achieve a delicate balance between effective hemostasis and pathological conditions such as thrombosis, one of the major causes of death in the world. Because the components of the hemostatic process interact in complex ways, how the various components work together to implement fast, effective and stable responses to vascular injury cannot be fully understood using traditional experimental methods alone—quantitative models are required. While a significant amount of effort has been devoted to developing mathematical models for many individual subsystems of hemostasis in isolation, only a model that adequately captures the complete interactive nature of the subsystems can provide a meaningful representation of the entire process. However, developing a faithful mathematical representation of known mechanistic details of the entire hemostatic process using standard modeling approaches will produce a model containing an inordinately large number of variables and an even larger number of unknown parameters. An alternative conceptual paradigm is required if the important complex details are to be represented adequately, with sufficient fidelity, and in mathematically tractable form.

Our proposed approach is based on the premise that from a process engineering perspective, hemostasis is mediated by an automatic biological control system; an engineering control system representation will therefore provide a structure for organizing information efficiently in terms of the control system components as “functional modules,” thereby facilitating systematic analysis of the complete hemostatic process as a combination of the component modules.

We will present a high-level engineering control system block diagram for hemostasis as the foundational basis of the holistic model and then focus on one subsystem, the process actuator block, which represents how the central physiological process of platelet aggregation is implemented. We will present results showing the dynamic characteristics predicted by our model, compare the model simulations to experimental data, and discuss future plans for completing the model development and using the complete model for systematic analysis of the overall process of hemostasis.