3 years ago

Normal and pathological dynamics of platelets in humans

Jacques Bélair, Morgan Craig, Gabriel P. Langlois, Sean R. Sinclair, Thibault Moulin, Joseph M. Mahaffy, Michael C. Mackey, Antony R. Humphries, Liangliang Wang

Abstract

We develop a 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 model fits to the existing data for both platelet counts and thrombopoietin levels by changing four parameters that have physiological correlates. Our results indicate that the primary change in cyclic thrombocytopenia is an 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 contributes to the understanding of the origin of cyclic thrombocytopenia as well as extending the modeling of thrombopoiesis.

Publisher URL: https://link.springer.com/article/10.1007/s00285-017-1125-6

DOI: 10.1007/s00285-017-1125-6

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