@article {Menezeseaaf5045, author = {Menezes, Amor A. and Vilardi, Ryan F. and Arkin, Adam P. and Cohen, Mitchell J.}, title = {Targeted clinical control of trauma patient coagulation through a thrombin dynamics model}, volume = {9}, number = {371}, elocation-id = {eaaf5045}, year = {2017}, doi = {10.1126/scitranslmed.aaf5045}, publisher = {American Association for the Advancement of Science}, abstract = {In the setting of severe trauma, some patients develop acute traumatic coagulopathy, impaired coagulation that can occur in response to shock. For patients who are already bleeding and then develop coagulopathy, there is no time to carefully perform laboratory analysis, and blood products are usually transfused according to standardized protocols. Because these protocols are not tailored to individual patients or injuries, this can result in insufficient or excessive blood product transfusions, which contribute to the high risk of mortality. Using dynamic modeling, Menezes et al. demonstrated a method for calculating each patient{\textquoteright}s transfusion requirements using only laboratory values that can be easily and quickly obtained in the emergency setting, which should allow for individually tailored resuscitation.We present a methodology for personalizing the clinical treatment of severely injured patients with acute traumatic coagulopathy (ATC), an endogenous biological response of impaired coagulation that occurs early after trauma and shock and that is associated with increased bleeding, morbidity, and mortality. Despite biological characterization of ATC, it is not easily or rapidly diagnosed, not always captured by slow laboratory testing, and not accurately represented by coagulation models. This lack of knowledge, combined with the inherent time pressures of trauma treatment, forces surgeons to treat ATC patients according to empirical resuscitation protocols. These entail transfusing large volumes of poorly characterized, nontargeted blood products that are not tailored to an individual, the injury, or coagulation dynamics. Massive transfusion mortality remains at 40 to 70\% in the best of trauma centers. As an alternative to blunt treatments, time-consuming tests, and mechanistic models, we used dynamical systems theory to create a simple, biologically meaningful, and highly accurate model that (i) quickly forecasts a driver of downstream coagulation, thrombin concentration after tissue factor stimulation, using rapidly measurable concentrations of blood protein factors and (ii) determines the amounts of additional coagulation factors needed to rectify the predicted thrombin dynamics and potentially remedy ATC. We successfully demonstrate in vitro thrombin control consistent with the model. Compared to another model, we decreased the mean errors in two key trauma patient parameters: peak thrombin concentration after tissue factor stimulation and the time until this peak occurs. Our methodology helps to advance individualized resuscitation of trauma-induced coagulation deficits.}, issn = {1946-6234}, URL = {https://stm.sciencemag.org/content/9/371/eaaf5045}, eprint = {https://stm.sciencemag.org/content/9/371/eaaf5045.full.pdf}, journal = {Science Translational Medicine} }