Normal and pathological dynamics of platelets in humans
Abstract
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.
Keywords
Cite
@article{arxiv.1608.02806,
title = {Normal and pathological dynamics of platelets in humans},
author = {Gabriel P. Langlois and Morgan Craig and Antony R. Humphries and Michael C. Mackey and Joseph M. Mahaffy and Jacques Bélair and Thibault Moulin and Sean R. Sinclair and Liangliang Wang},
journal= {arXiv preprint arXiv:1608.02806},
year = {2021}
}