title: Multiscale models of thrombogenesis.
abstract: To restrict the loss of blood follow from the rupture of blood vessels, the human body rapidly forms a clot consisting of platelets and fibrin. However, to prevent pathological clotting within vessels as a result of vessel damage, the response must be regulated. Clots forming within vessels (thrombi) can restrict the flow of blood causing damage to tissues in the flow field. Additionally, fragments dissociating from the primary thrombus (emboli) may lodge and clog vessels in the brain (causing ischemic stroke) or lungs (resulting in pulmonary embolism). Pathologies related to the obstruction of blood flow through the vasculature are the major cause of mortality in the United States. Venous thromboembolic disease alone accounts for 900,000 hospitalizations and 300,000 deaths per year and the incidence will increase as the population ages (Wakefield et al. J Vasc Surg 2009, 49:1620-1623). Thus, understanding the interplay between the many processes involved in thrombus development is of significant biomedical value. In this article, we first review computational models of important subprocesses of hemostasis/thrombosis including coagulation reactions, platelet activation, and fibrin assembly, respectively. We then describe several multiscale models integrating these subprocesses to simulate temporal and spatial development of thrombi. The development of validated computational models and predictive simulations will enable one to explore how the variation of multiple hemostatic factors affects thrombotic risk providing an important new tool for thrombosis research.
authors.affiliation: Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN, USA.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Xu
authors.forename: Oleg
authors.initials: O
authors.lastname: Kim
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kamocka
authors.forename: Elliot D
authors.initials: ED
authors.lastname: Rosen
authors.forename: Mark
authors.initials: M
authors.lastname: Alber
mesh_terms: D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D008954:Models, Biological; D015539:Platelet Activation; D013927:Thrombosis / Q000097:blood* / Q000473:pathology
chemical_list: D005337:Fibrin