Normal and pathological dynamics of platelets in humans

TL;DR

This paper presents a detailed mathematical model of human platelet dynamics, explaining both normal and cyclic thrombocytopenia conditions by analyzing parameter changes and their physiological implications.

Contribution

It introduces a comprehensive model that captures the dynamics of platelets, megakaryocytes, and thrombopoietin, and identifies key parameters involved in cyclic thrombocytopenia.

Findings

Model fits well with clinical data on platelet counts and thrombopoietin levels.

Cyclic thrombocytopenia linked to disruption of thrombopoietin receptor function.

Primary cause involves interference with thrombopoietin receptor, affecting platelet production.

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.