  We develop a comprehensive mathematical model of platelet, megakaryocyte, and
thrombopoietin dynamics in humans. We show that there is a single stationary
solution that can undergo a Hopf bifurcation, and use this information to
investigate both normal and pathological platelet production, specifically
cyclic thrombocytopenia. Carefully estimating model parameters from laboratory
and clinical data, we then argue that a subset of parameters are involved in
the genesis of cyclic thrombocytopenia based on clinical information. We
provide excellent model fits to the existing data for both platelet counts and
thrombopoietin levels by changing six parameters that have physiological
correlates. Our results indicate that the primary change in cyclic
thrombocytopenia is a major interference with or destruction of the
thrombopoietin receptor with secondary changes in other processes, including
immune-mediated destruction of platelets and megakaryocyte deficiency and
failure in platelet production. This study makes a major contribution to the
understanding of the origin of cyclic thrombopoietin as well as significantly
extending the modeling of thrombopoiesis.
