Systems biology to predict blood function

Abstract

Systems biology seeks to provide a quantitative framework to understand blood as a reactive biological fluid whose function is dictated by prevailing haemodynamics, vessel wall characteristics, platelet metabolism, numerous coagulation factors in plasma, and small molecules released during thrombosis. The hierarchical nature of thrombosis requires analysis of adhesive bond dynamics of activated platelets captured from a flow field to a growing thrombus boundary along with the simultaneous assembly of the coagulation pathway. Several kinetic models of protease cascades have been developed. A full bottom-up model of platelet intracellular metabolism is now available to simulate the metabolism of resting platelets and platelets exposed to activators. Monte Carlo algorithms can finally accommodate platelet reaction, dispersion, and convection for full simulation of platelet deposition and clotting under flow. For clinical applications, the systems biology prediction of patient-specific pharmacological response requires the final assembly of platelet intracellular metabolism models with coagulation protease network models. © 2009 International Society on Thrombosis and Haemostasis.