A Mathematical Model, Describing the Kinetic Behaviour of the Thrombopoietic System in Mice and Rats

Abstract

A mathematical model of thrombopoiesis in small rodents, principally rats, is presented. It is a compartmental model, consisting of seven compartments, which contain the following cell populations: early megakaryocyte progenitor cells, late megakaryocyte progenitor cells, megakaryocytes of ploidy classes 8N, 16N, 32N and 64N, and platelets. Signals for feedback regulation are derived from the platelet compartment and from all megakaryocyte compartments. The main characteristic of the model is its ability to simulate megakaryocyte ploidy and volume distribution. Platelet number and the ploidy distribution of megakaryocytes after acute and chronic disturbances in the platelet compartment were simulated and were found to approximate experimental data published in the literature. The kinetic parameters for the progenitor cell compartment, which were derived from published in vitro data, were sufficient to stimulate the platelet number after administration of hydroxyurea and 5-fluorouracil. The proposed model is capable of reproducing the reactions of the system to several experimental disturbances in the thromobopoietic lineage, but the action of agents such as radiation, which cause damage to the stem cells or to other lineages, cannot be simulated.