Systems Approaches to Understanding and Monitoring Coagulopathy in Trauma

Trauma-induced coagulopathy is the catastrophic malfunction of blood coagulation after massive injuries.  We investigate coagulopathy using a combination of systems biology modeling and analysis of clinical data.  At the same time, we are developing next-generation real-time protein biomarker diagnostic capabilities, to monitor and control critical blood proteins in coagulopathic patients. The goal of our systems biology effort is to understand coagulopathy and to use this understanding to be able to predict the effects of possible therapies on patient outcome.  To this end we use two approaches: bottom-up and top-down.  In the bottom-up approach we simulate a damaged blood vessel using a partial differential equation model of blood chemistry and flow, validated through microfluidic experiments, to model the effects of an injury on blood chemistry.   In the top-down approach we mine clinical data from trauma centers with machine-learning techniques to identify the measurable variables that are most closely associated with a healthy outcome.  Complementary to this work is the development of novel biosensor technologies. Our goal is to create a universal sensing platform to monitor changes in blood proteins and other biomarkers as they occur in real-time during trauma-induced coagulopathy. Our approach is called the Microfluidic Electrochemical Detector for In Vivo Continuous monitoring (MEDIC) which for the first time enables both rapid quantitative measurements of specific blood factors as well as real-time operation in whole blood.