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

Vascular trauma is the leading cause of death in military environments and hemorrhage is the major preventable cause of mortality among trauma patients. Recent experience from Iraq and Afghanistan has demonstrated improved 24-h and 30-day survival in combat casualties requiring early massive transfusion. Unlike plasma and erythrocytes, 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 platelet storage lesion (PSL). In Phase I we have developed multiscale computational tools integrating systems biology, biophysics and physiology to model the deleterious effects of platelet storage and to explore novel storage methods. The model integrates the bag-scale analysis of storage media chemistry, heat transfer and mixing with the cell-scale platelet systems biology. The model, partially validated on test data, correctly predicts metabolic shifts, changes in platelet shape, fall of media pH and other experimentally observed effects. Metabolic and functional advantages of 40C storage and temperature cycling have also been confirmed. In Phase II we plan a complementary computational and experiment effort to further develop the PSL model and to validate it on benchmark test data. The model will be used to optimize the storage conditions and to