Makin2013 - Blood coagulation cascade model
Mathematical model of the blood coagulation system including lipid binding sites, meizothrombin, thrombomodulin, cleaved and light peptide chain Va species and Heparin.
- A hybrid-system model of the coagulation cascade: simulation, sensitivity, and validation.
- Makin JG, Narayanan S
- Journal of bioinformatics and computational biology , 10/ 2013 , Volume 11 , Issue 5 , pages: 1342004
- Department of Electrical Engineering and Computer Science, University of California, Berkeley, USA , International Computer Science Institute, Berkeley, CA 94720, USA.
- The process of human blood clotting involves a complex interaction of continuous-time/continuous-state processes and discrete-event/discrete-state phenomena, where the former comprise the various chemical rate equations and the latter comprise both threshold-limited behaviors and binary states (presence/absence of a chemical). Whereas previous blood-clotting models used only continuous dynamics and perforce addressed only portions of the coagulation cascade, we capture both continuous and discrete aspects by modeling it as a hybrid dynamical system. The model was implemented as a hybrid Petri net, a graphical modeling language that extends ordinary Petri nets to cover continuous quantities and continuous-time flows. The primary focus is simulation: (1) fidelity to the clinical data in terms of clotting-factor concentrations and elapsed time; (2) reproduction of known clotting pathologies; and (3) fine-grained predictions which may be used to refine clinical understanding of blood clotting. Next we examine sensitivity to rate-constant perturbation. Finally, we propose a method for titrating between reliance on the model and on prior clinical knowledge. For simplicity, we confine these last two analyses to a critical purely-continuous subsystem of the model.