Modeling the Thrombopoietic Effects of Burn

Abstract

Our group is currently developing physiologically based models to understand the impact of radiation combined injury and aid in casualty predictions for catastrophic scenarios. We have developed a model that describes the impact of burn on thrombopoiesis with the aim of integrating it into an existing radiation-effects model. Thrombocytopenia can be a life-threatening condition due to the role of platelets in hemostasis and the immune response. Thermal injury is known to cause thrombocytopenia as well as a subsequent thrombocytosis. Key biological effects of burn were identified, mathematically interpreted, and implemented. These effects include a decreased platelet lifespan and an increased repopulation rate due to increased levels of thrombopoietin within the system. The model predicts platelet and precursor cell concentrations over time, providing details on time, magnitude, and duration of thrombocytopenias. Parameter values were obtained through both the analysis of experimental data and the optimization of the model to observational data on platelet counts following burn. The model was subsequently validated against other datasets and simulations were performed to better understand the characteristics of the model. The model describes the effects of thermal injury on thrombopoiesis, providing realistic predictions that reflect the trends observed in platelet concentrations.