Section: New Results

Mathematical modeling of platelet production

• In [10], we analyze the existence of oscillating solutions and the asymptotic convergence for a nonlinear delay differential equation arising from the modeling of platelet production. We consider four different cell compartments corresponding to different cell maturity levels: stem cells, megakaryocytic progenitors, megakaryocytes, and platelets compartments, and the quantity of circulating thrombopoietin (TPO), a platelet regulation cytokine.

• In [11], we analyze the stability of a differential equation with two delays originating from a model for a population divided into two subpopulations, immature and mature, and we apply this analysis to a model for platelet production. The dynamics of mature individuals is described by the following nonlinear differential equation with two delays: $x\prime \left(t\right)=-\lambda x\left(t\right)+g\left(x(t-{\tau }_1)\right)-g\left(x(t-{\tau }_1-{\tau }_2)\right)e^{-\lambda {\tau }_2}$ . The method of $D$-decomposition is used to compute the stability regions for a given equilibrium. The center manifold theory is used to investigate the steady-state bifurcation and the Hopf bifurcation. Similarly, analysis of the center manifold associated with a double bifurcation is used to identify a set of parameters such that the solution is a torus in the pseudo- phase space. Finally, the results of the local stability analysis are used to study the impact of an increase of the death rate γ or of a decrease of the survival time ${\tau }_2$ of platelets on the onset of oscillations. We show that the stability is lost through a small decrease of survival time (from $8.4$ to 7 days), or through an important increase of the death rate (from $0.05$ to $0.625$ days${}^{-1}$).

• In [12], we analyze the stability of a system of differential equations with a threshold-defined delay arising from a model for platelet production. We consider a maturity-structured population of megakaryocyte progenitors and an age-structured population of platelets, where the cytokine thrombopoietin (TPO) increases the maturation rate of progenitors. Using the quasi-steady-state approximation for TPO dynamics and the method of characteristics, partial differential equations are reduced to a system of two differential equations with a state-dependent delay accounting for the variable maturation rate. We start by introducing the model and proving the positivity and boundedness of the solutions. Then we use a change of variables to obtain an equivalent system of two differential equations with a constant delay, from which we prove existence and uniqueness of the solution. As linearization around the unique positive steady state yields a transcendental characteristic equation of third degree, we introduce the main result, a new framework for stability analysis on models with fixed delays. This framework is then used to describe the stability of the megakaryopoiesis with respect to its parameters. Finally, with parameters being obtained and estimated from data, we give an example in which oscillations appear when the death rate of progenitors is increased 10-fold.