Paper Info
Title
Computational Modeling Of Blood Component Transport Related To Coronary Artery Thrombosis In Kawasaki Disease
Abstract
Coronary artery thrombosis is the major risk associated with Kawasaki disease (KD). Long-term management of KD patients with persistent aneurysms requires a thrombotic risk assessment and clinical decisions regarding the administration of anticoagulation therapy. Computational fluid dynamics has demonstrated that abnormal KD coronary artery hemodynamics can be associated with thrombosis. However, the underlying mechanisms of clot formation are not yet fully understood. Here we present a new model incorporating data from patient-specific simulated velocity fields to track platelet activation and accumulation. We use a system of Reaction-Advection-Diffusion equations solved with a stabilized finite element method to describe the evolution of non-activated platelets and activated platelet concentrations [AP], local concentrations of adenosine diphosphate (ADP) and poly-phosphate (PolyP). The activation of platelets is modeled as a function of shear-rate exposure and local concentration of agonists. We compared the distribution of activated platelets in a healthy coronary case and six cases with coronary artery aneurysms caused by KD, including three with confirmed thrombosis. Results show spatial correlation between regions of higher concentration of activated platelets and the reported location of the clot, suggesting predictive capabilities of this model towards identifying regions at high risk for thrombosis. Also, the concentration levels of ADP and PolyP in cases with confirmed thrombosis are higher than the reported critical values associated with platelet aggregation (ADP) and activation of the intrinsic coagulation pathway (PolyP). These findings suggest the potential initiation of a coagulation pathway even in the absence of an extrinsic factor. Finally, computational simulations show that in regions of flow stagnation, biochemical activation, as a result of local agonist concentration, is dominant. Identifying the leading factors to a pro-coagulant environment in each case-mechanical or biochemical-could help define improved strategies for thrombosis prevention tailored for each patient.Author Summary Computational studies aiming to model thrombosis often rely on an arterial wall injury. Collagen and other extracellular matrix components are exposed to the bloodstream, which facilitates platelet adhesion to the wall and subsequent clot formation. However, these models are not adequate to explain thrombosis in other settings where even in the absence of a focal lesion, clots may still form under certain flow conditions. Coronary artery aneurysm thrombosis following KD is an example of the need to understand the mechanisms of thrombus initiation in the absence of an extrinsic factor. This study provides a new framework to investigate thrombus initiation in KD from a patient-specific perspective, which integrates fluid mechanics and biochemistry and which could help quantify the pro-coagulant environment induced by the aneurysm and become a predictive tool. The work presented here has broad relevance to other clinical situations where flow stagnation and transport are driving factors in thrombus formation.
Year
DOI
Venue
2021
10.1371/journal.pcbi.1009331
PLOS COMPUTATIONAL BIOLOGY
DocType
Volume
Issue
Journal
17
9
ISSN
Citations 
PageRank 
1553-734X
0
0.34
References 
Authors
0
7
Name
Order
Citations
PageRank
Noelia Grande Gutiérrez100.34
Mark Alber200.68
Andrew Kahn300.68
Jane C. Burns4111.40
Mathew Mathew500.34
Brian W McCrindle600.34
Alison Marsden7528.83