Systems Biology Based Tools for Modeling Platelet Storage Lesion for Optimal Blood Transfusions

Trauma is the leading cause of death in civilian and military environments and acute hemorrhage contributes to a large portion of these fatalities. Recent experience from Iraq and Afghanistan has demonstrated the crucial role of blood products in the care of critically injured soldiers. Unlike plasma and red blood cells, which can be cold stored for longer time periods, platelets can be safely stored only for few days before they develop a condition known as storage lesion. Better understanding of the mechanisms and molecular pathways involved in this damage could help in the development of novel storage methods and improved platelet functions. We propose to develop an integrated systems biology- and physiology- based computational tools to model the deleterious effects of platelet storage and to explore novel methods of storage and protection. A multiscale kinetic model involving platelet energy metabolism, signaling pathways and biophysical model will be developed to analyze the mechanisms of lesion development and methods of platelet protection. The model will be validated on published experimental and/or clinical data. The effects of storage temperature, media composition and selected inhibitors will be investigated and model will be used to develop optimal storage conditions. The final software framework and validated models will be delivered to the Army.