A numerical analysis model for the interpretation of in vivo platelet consumption data

Unlike anemias, most thrombocytopenias cannot be separated into those due to impaired production and those due to accelerated consumption. While rapid clearance of labeled platelets from the bloodstream can be followed in thrombocytopenic individuals, no model exists for quantitatively inferring from autologous or allogeneic platelet consumption data what changes in random consumption, lifespan dependent consumption, and platelet production rate may have caused the thrombocytopenia. Here we describe a numerical analysis model which resolves these issues. The model applies three parameter values (a random consumption rate constant, a lognormally-distributed platelet lifespan, and the standard deviation of the latter) to a matrix comprising a series of platelet cohorts which are sequentially produced and fractionally consumed in a series of time intervals. The cohort platelet counts achieved after equilibration of production and consumption both enumerate the population age distribution and sum to the population platelet count. Continued platelet consumption after production is halted then serves to model in vivo platelet consumption data, with consumption rate in the first such interval defining the equilibrium platelet production rate. We use a least squares fitting procedure to find parameter values which best fit observed platelet consumption data obtained in WT and thrombocytopenic WASP(-) mice. Equilibrium platelet age distributions are then 'grafted' into the matrix to allow modeling of the consumption of WT platelets in WASP(-) recipients, and vice versa. The optimal parameter values obtained indicate that random WT platelet consumption accounts for a larger fraction of platelet turnover than was previously suspected. Platelet WASP deficiency accelerates random consumption, and a trans effect of recipient WASP deficiency contributes to this. Application of the model to clinical data will allow distinctions to be made between thrombocytopenias due primarily to impaired platelet production and those due to acceleration of random or lifespan-dependent platelet consumption.