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Description
Blood is one of the most important components of the body that are essential to the survival of an organism. Maintaining the processes of hematopoiesis in homeostasis are vital for the correct functioning of the body. The mechanisms regulating hematopoiesis are mostly well-controlled with complex feedback systems of cytokines and numerous monitoring receptors. Nonetheless, disturbances or abnormalities in this regulation process can have harmful consequences for the organism. In this thesis, we model the normal and pathological dynamics of megakaryocyte, platelet, and thrombopoietin, with an interest in cyclic thrombocytopenia (CT), a rare blood disorder, whose pathogenesis is still not well understood. Our model shows the existence of a unique positive equilibrium, and a stability analysis indicates that it can undergo a Hopf bifurcation.The parameters used in the model are obtained from clinical and laboratory data, while some were found through fitting. An extensive sensitivity analysis was performed to determine the model response to changes. The mathematical model proposed in this paper is able to reproduce oscillations by changing four parameters based on the possible causes for CT suggested by clinical literature, and these changes are fit to patient data of both platelets and thrombopoietin. The results indicate that the primary cause of cyclic thrombocytopenia is a disturbance or disruption of the thrombopoietin control mechanisms, with secondary causes being increased platelet destruction and deficiencies in megakaryocyte production. These results should offer more insight into the pathogenesis of cyclic thrombocytopenia and help guide experimental biologists to perform further research into the influence thrombopoietin and its receptors.
