Abstract
Two platelet activation models were studied with respect to uncertainties of model parameters and variables. The sensitivity was assessed using two direct/deterministic approaches as well as the statistical Monte Carlo method. The first two, are linear in character whereas the latter is non-linear. The platelet activation models were applied on platelets moving within an extracorporeal centrifugal blood pump. The phenomenological, Lagrangian stress- and time-based power law-based models under consideration, have experimentally calibrated parameters and the stress expressed in a scalar form. The sensitivity of the model with respect to model parameters and the expression of the scalar stress was examined focusing on a smaller group of platelets associated with an elevated risk of activation. The results showed a high disparity between the models in terms of platelet activation state, found to depend on the platelets’ trajectory in the pump and the expression used for the scalar stress. Monte Carlo statistics was applied to the platelets at risk for activation and not to the entire platelet population. The method reveals the non-linear sensitivity of the activation models. The results imply that power-law based models have a restricted range of validity. The conclusions of this study apply to both platelet activation and hemolysis models.
Highlights
Development of artificial support of organ function or replacement of organs has been an important objective for a long time
The sensitivity of two platelet activation models with respect to model parameters and the stress acting on the platelets were studied for a uniform stress field and the flow in a centrifugal pump
The linear sensitivity of the models was determined by computing the derivative of the Platelet Activation State (PAS) parameter with respect to model parameters and the scalar stress and by analyzing the contribution of the different terms in the model to the time rate of change of PAS
Summary
Development of artificial support of organ function or replacement of organs has been an important objective for a long time. In cardio-respiratory support that is limited in time (from less than a week to months), i.e. extracorporeal membrane oxygenation (ECMO), common problems are thrombus formation[1] and increased risk of patient bleeding[2] Such complications are the main reason why organ transplant or organic components are most often preferred. When coated by a heparin-based lining reducing thrombin and factor X activation[5], platelet activation induced by the artificial surfaces lessens This measure does not completely eliminate the rate of complications[4]. For flows deviating from the calibrated conditions, validation of platelet activation models remains difficult This is mainly due to the lack of detailed flow information in terms of the temporal and spatial variations of the stress tensor components and blood constituent distribution. Two different flow setups were studied; a uniform stress field investigating the sensitivity of the different platelet activation models under steady as well as time-depended stress and the activation model sensitivity for the flow in a centrifugal blood pump
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