A fibrin enhanced thrombosis model for medical devices operating at low shear regimes or large surface areas

Abstract

Over the past decade, much of the development of computational models of device-related thrombosis has focused on platelet activity. While those models have been successful in predicting thrombus formation in medical devices operating at high shear rates (> 5000 s−1), they cannot be directly applied to low-shear devices, such as blood oxygenators and catheters, where emerging information suggest that fibrin formation is the predominant mechanism of clotting and platelet activity plays a secondary role. In the current work, we augment an existing platelet-based model of thrombosis with a partial model of the coagulation cascade that includes contact activation of factor XII and fibrin production. To calibrate the model, we simulate a backward-facing-step flow channel that has been extensively characterized in-vitro. Next, we perform blood perfusion experiments through a microfluidic chamber mimicking a hollow fiber membrane oxygenator and validate the model against these observations. The simulation results closely match the time evolution of the thrombus height and length in the backward-facing-step experiment. Application of the model to the microfluidic hollow fiber bundle chamber capture both gross features such as the increasing clotting trend towards the outlet of the chamber, as well as finer local features such as the structure of fibrin around individual hollow fibers. Our results are in line with recent findings that suggest fibrin production, through contact activation of factor XII, drives the thrombus formation in medical devices operating at low shear rates with large surface area to volume ratios.

Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs

“…The heterogeneous distribution of the clots may be a result of different flow conditions within the ML. Both, areas with high shear rates (at the immediate entrance of the PLS ML) ( 1 , 26 ) and stagnation points ( 27 ) (reduced blood flow attributed to the weaning process) are discussed. However, this mechanism is questionable, since clot localization within other used PLS MLs after weaning presented various distribution patterns ( 1 ).…”

clotFoam: An open-source framework to simulate blood clot formation under arterial flow

“…A few in-house codes of clotting models are freely available [ 20 , 21 ], but are quite model-specific and not necessarily made for other researchers to easily build upon. In this work we present clotFoam, a cell-centered finite volume solver that provides a flexible framework for simulating and easily extending a reduced model of blood clotting under flow.…”

Effects of cardiac function alterations on the risk of postoperative thrombotic complications in patients receiving endovascular aortic repair

“…By modeling the process of hemodynamics and mass transport in the coagulation cascade, the patient-specific patterns of formation and distribution of intraluminal/intra-prosthetic thrombus formation can be simulated or predicted with acceptable accuracy ( Menichini and Xu, 2016 ; Sun et al, 2021 ). Based on different thrombus initialization mechanisms, numerous computational models for thrombus formation have been developed in literature ( Fogelson, 1992 ; Wu et al, 2020 ; Zheng et al, 2020 ; Bouchnita et al, 2021 ; Grande Gutiérrez et al, 2021 ; Méndez Rojano et al, 2022 ; Shankar et al, 2022 ). However, the explicit effects of cardiac functions on thrombus formation were not yet well addressed.…”