In Vitro and In Silico Characterization of the Aggregation of Thrombi on Ventricular Assist Device Cannula

The unacceptably high stroke rate of HeartMate III VAD without signs of adherent pump thrombosis is hypothesized to be the result of the thrombi originating on the inflow cannula, ingesting and ejecting emboli from the VAD. Therefore, inflow cannula thrombosis has been an emerging focus. The inflow cannula of contemporary VADs, which incorporate both polished and rough regions serve as useful benchmarks to study the effects of roughness and shear on thrombogenesis. An in vitro study was conducted to emulate the micro-hemodynamic condition on a sintered inflow cannula, and to observe the deposition and detachment patterns. Together with a computational fluid dynamic tool, this study aimed to provide insight into the optimization of inflow cannula and potentially reducing adverse neurological events due to upstream thrombus

Introducing the pro-coagulant contact system in the numerical assessment of device-related thrombosis

International audienceThrombosis is a major concern in blood-coated medical devices. Contact activation, which is the initial part of the coagulation cascade in device-related thrombosis, is not considered in current thrombus formation models. In the present study, pro-coagulant reactions including the contact activation system are coupled with a fluid solver in order to evaluate the potential of the contact system to initiate thrombin production. The biochemical/fluid model is applied to a backward facing step configuration, a flow configuration that frequently appears in medical devices. In contrast to the in vivo thrombosis models in which a specific thrombotic zone (injury region) is set a priori by the user to initiate the coagulation reaction, a reactive surface boundary condition is applied to the whole device wall. Simulation results show large thrombin concentration in regions related to recirculation zones without the need of an a priori knowledge of the thrombus location. The numerical results align well with the regions prone to thrombosis observed in experimental results reported in the literature. This approach could complement throm-bus formation models that take into account platelet activity and thrombus growth to optimize a wide range of medical devices

Kinetics of the coagulation cascade including the contact activation system: sensitivity analysis and model reduction

International audienceThrombus formation is one of the main issues in the development of blood-contacting medical devices. This article focuses on the modeling of one aspect of thrombosis, the coagulation cascade, which is initiated by the contact activation at the device surface and forms thrombin. Models exist representing the coagulation cascade by a series of reactions, usually solved in quiescent plasma. However, large parameter uncertainty involved in the kinetic models can affect the predictive capabilities of this approach. In addition, the large number of reactions of the kinetic models prevents their use in the simulation of complex flow configurations encountered in medical devices. In the current work, both issues are addressed to improve the applicability and fidelity of kinetic models. A sensitivity analysis is performed by two different techniques to identify the most sensitive parameters of an existing detailed kinetic model of the coagulation cascade. The results are used to select the form of a novel reduced model of the coagulation cascade which relies on eight chemical reactors only. Then, once its parameters have been calibrated thanks to the Bayesian inference, this model shows good predictive capabilities for different initial conditions

Kinetics of the coagulation cascade including the contact activation system: Sensitivity analysis and model reduction

International audienceThrombus formation is one of the main issues in the development of blood-contacting medical devices. This article focuses on the modeling of one aspect of thrombosis, the coagulation cascade, which is initiated by the contact activation at the device surface and forms thrombin. Models exist representing the coagulation cascade by a series of reactions, usually solved in quiescent plasma. However, large parameter uncertainty involved in the kinetic models can affect the predictive capabilities of this approach. In addition, the large number of reactions of the kinetic models prevents their use in the simulation of complex flow configurations encountered in medical devices. In the current work, both issues are addressed to improve the applicability and fidelity of kinetic models. A sensitivity analysis is performed by two different techniques to identify the most sensitive parameters of an existing detailed kinetic model of the coagulation cascade. The results are used to select the form of a novel reduced model of the coagulation cascade which relies on eight chemical reactors only. Then, once its parameters have been calibrated thanks to the Bayesian inference, this model shows good predictive capabilities for different initial conditions

Thrombus growth in backward facing step reattachment point.

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Model parameters used in the bovine BFS simulation.

Model parameters used in the bovine BFS simulation.</p

Fig 6 -

A) Simulation domain comprised a quarter of the full geometry, taking advantage of device symmetries. Boundaries colored blue were set as symmetry planes, and boundaries colored red correspond to reactive boundary conditions. B) Mesh boundary layers at hollow fibers in the microfluidic chamber.</p