Uncertainty quantification of a thrombosis model considering the clotting assay PFA-100

Abstract

Mathematical models of thrombosis are currently used to study clinical scenarios of pathological thrombus formation. Most of these models involve inherent uncertainties that must be assessed to increase the confidence in model predictions and identify avenues of improvement for both thrombosis modeling and anti-platelet therapies. In this work, an uncertainty quantification analysis of a multi-constituent thrombosis model is performed considering a common assay for platelet function (PFA-100). The analysis is performed using a polynomial chaos expansion as a parametric surrogate for the thrombosis model. The polynomial approximation is validated and used to perform a global sensitivity analysis via computation of Sobol' coefficients. Six out of fifteen parameters were found to be influential in the simulation variability considering only individual effects. Nonetheless, parameter interactions are highlighted when considering the total Sobol' indices. In addition to the sensitivity analysis, the surrogate model was used to compute the PFA-100 closure times of 300,000 virtual cases that align well with clinical data. The current methodology could be used including common anti-platelet therapies to identify scenarios that preserve the hematological balance.