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      An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms

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          Abstract

          Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development.

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          Most cited references44

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            Microparticles in hemostasis and thrombosis.

            Blood contains microparticles (MPs) derived from a variety of cell types, including platelets, monocytes, and endothelial cells. In addition, tumors release MPs into the circulation. MPs are formed from membrane blebs that are released from the cell surface by proteolytic cleavage of the cytoskeleton. All MPs are procoagulant because they provide a membrane surface for the assembly of components of the coagulation protease cascade. Importantly, procoagulant activity is increased by the presence of anionic phospholipids, particularly phosphatidylserine (PS), and the procoagulant protein tissue factor (TF), which is the major cellular activator of the clotting cascade. High levels of platelet-derived PS(+) MPs are present in healthy individuals, whereas the number of TF(+), PS(+) MPs is undetectable or very low. However, levels of PS(+), TF(+) MPs are readily detected in a variety of diseases, and monocytes appear to be the primary cellular source. In cancer, PS(+), TF(+) MPs are derived from tumors and may serve as a useful biomarker to identify patients at risk for venous thrombosis. This review will summarize our current knowledge of the role of procoagulant MPs in hemostasis and thrombosis.
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              Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis.

              Hemostasis requires both platelets and the coagulation system. At sites of vessel injury, bleeding is minimized by the formation of a hemostatic plug consisting of platelets and fibrin. The traditional view of the regulation of blood coagulation is that the initiation phase is triggered by the extrinsic pathway, whereas amplification requires the intrinsic pathway. The extrinsic pathway consists of the transmembrane receptor tissue factor (TF) and plasma factor VII/VIIa (FVII/FVIIa), and the intrinsic pathway consists of plasma FXI, FIX, and FVIII. Under physiological conditions, TF is constitutively expressed by adventitial cells surrounding blood vessels and initiates clotting. In addition so-called blood-borne TF in the form of cell-derived microparticles (MPs) and TF expression within platelets suggests that TF may play a role in the amplification phase of the coagulation cascade. Under pathologic conditions, TF is expressed by monocytes, neutrophils, endothelial cells, and platelets, which results in an elevation of the levels of circulating TF-positive MPs. TF expression within the vasculature likely contributes to thrombosis in a variety of diseases. Understanding how the extrinsic pathway of blood coagulation contributes to hemostasis and thrombosis may lead to the development of safe and effective hemostatic agents and antithrombotic drugs.
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                Author and article information

                Journal
                Front Physiol
                Front Physiol
                Front. Physio.
                Frontiers in Physiology
                Frontiers Research Foundation
                1664-042X
                20 July 2012
                2012
                : 3
                : 266
                Affiliations
                [1] 1simpleDepartment of Solid Mechanics, School of Engineering Sciences, KTH Royal Institute of Technology Stockholm, Sweden
                [2] 2simpleMechanics Division, National Institute of Metrological Research Turin, Italy
                [3] 3simpleDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet Stockholm, Sweden
                Author notes

                Edited by: Rajat Mittal, Johns Hopkins University, USA

                Reviewed by: Haoxiang Luo, Vanderbilt University, USA; Daniel Goldman, The University of Western Ontario, Canada

                *Correspondence: Jacopo Biasetti, Department of Solid Mechanics, School of Engineering Sciences, KTH Royal Institute of Technology, Osquars Backe 1, SE-100 44 Stockholm, Sweden. e-mail: biasetti@ 123456kth.se

                This article was submitted to Frontiers in Computational Physiology and Medicine, a specialty of Frontiers in Physiology.

                Article
                10.3389/fphys.2012.00266
                3429042
                22934022
                8d2a321f-83eb-4d60-afcf-91972f8247fe
                Copyright © 2012 Biasetti, Spazzini, Swedenborg and Gasser.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 31 March 2012
                : 25 June 2012
                Page count
                Figures: 12, Tables: 6, Equations: 17, References: 70, Pages: 16, Words: 9759
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                coagulation cascade,intra-luminal thrombus,platelets,computational fluid dynamics,thrombin,convection-diffusion-reaction equations,abdominal aortic aneurysm,vortical structures

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