Regulation of Platelet Production: The Normal Response to Perturbation and Cyclical Platelet Disease

Cyclic thrombocytopenia with statistically significant neutrophil oscillations

“…These diseases are believed to arise from the interaction between the hematopoietic stem cell compartment and peripheral control mechanisms. However, because in CT fluctuations had been observed only in the platelets, a destabilization of a peripheral control mechanism was postulated to play a significant role in the genesis of this disorder 11, 20. Although the control of neutrophil production and the regulation of erythropoiesis have been the subject of numerous modeling studies, there have been fewer treating the regulation of platelets production.…”

“…Von Schulthess et al,23 noting the existence of oscillations in the platelet counts of normal humans, put forward a conceptually different model of thrombopoiesis, which was followed by Bélair and Mackey 24. Building on this work, Santillan et al20 refined the model attempting to understand cyclical thrombocytopenia, and this was subsequently modified by Apostu and Mackey10 and Langlois et al,25 again to understand the origins of cyclical thrombocytopenia. The latter modeling work has suggested that a defective TPO‐TPO receptor interaction may contribute to the pathogenesis.…”

Cell Modelling of Hematopoiesis

“…The most recent models in blood diseases in the literature are the so-called maturity-agetime structured models consisting of a system of partial differential equations describing instability of the cell population facing aplastic anemia [3,4,13,14]. Some other deterministic models using either systems of differential equations or age structured systems deal with cyclical neutropenia [5,6,16,17], thrombocytopenia [25,26], or chronic myelogenous leukemia [1,2,10,22,23,24]. It is important here to notice that most of the continuous models deal with density only while our approach in the paper is to consider a population of individual cells.…”

Delay Differential Equations and Autonomous Oscillations in Hematopoietic Stem Cell Dynamics Modeling

“…These disorders are considered as major suspects in causing periodic hematological diseases, such as chronic myelogenous leukemia [9,27,42,43,76,77], cyclical neutropenia [28,51,54], periodic auto-immune hemolytic anemia [18,65,67,69], and cyclical thrombocytopenia [16,79]. In some of these diseases, oscillations occur in all mature blood cells with the same period; in others, the oscillations appear in only one or two cell types.…”