Regulation of Platelet Production: The Normal Response to Perturbation and Cyclical Platelet Disease

An age-structured model for the regulation of platelet production is developed, and compared with both normal and pathological platelet production. We consider the role of thrombopoietin (TPO) in this process, how TPO affects the transition between megakaryocytes of various ploidy classes, and their individual contributions to platelet production. After the estimation of the relevant parameters of the model from both in vivo and in vitro data, we use the model to numerically reproduce the normal human response to a bolus injection of TPO. We further show that our model reproduces the dynamic characteristics of autoimmune cyclical thromobocytopenia if the rate of platelet destruction in the circulation is elevated to more than twice the normal value.