Modeling thrombus formation and growth

Abstract

The paper reviews the state-of-the-art in computational modeling of thrombus formation and growth and related phenomena including platelet margination, activation, adhesion, and embolization. Presently, there is a high degree of empiricism in the modeling of thrombus formation. Based on the experimentally observed physics, the review gives useful strategies for predicting thrombus formation and growth. These include determining blood components involved in atherosclerosis, effective blood viscosity, tissue properties, and methods proposed for boundary conditions. In addition to the guidelines, ongoing research on the effect of shear stress on platelet margination, activation and adhesion, and platelet-surface interactions are reviewed. Biotechnol. Bioeng. 2017;114: 2154-2172. © 2017 Wiley Periodicals, Inc.

Human blood platelets contract in perpendicular direction to shear flow

“…The shear rates vary greatly in the human body, from 5 to 10 s À1 in larger veins up to 2000 s À1 in small arteries. 7,8 Hence, platelets must attach, spread and contract under various conditions.…”

A density‐dependent FEM‐FCT algorithm with application to modeling platelet aggregation

“…In our previous works, we describe the methodology that enables the single cell (platelet) length scale to play a role in the model, i.e., through the phenomenological adhesion, cohesion, and hindered transport. There are other approaches to modeling platelet aggregation where each platelet is individually modeled as a discrete object, such as the immersed boundary method, Cellular Potts methods, Lattice Boltzmann methods, or dissipative particle dynamics; with these methods, each platelet is usually modeled as a discrete structure that interacts with the surrounding fluid, and in some instances with fluid on its interior. These modeling techniques have been instrumental in learning about platelet‐platelet and platelet‐wall interactions and platelet margination.…”

“…Most computational models of platelet aggregation, including our previous work, were used to study intravascular clot formation, where there is no leakage of blood from the vessel ; this scenario models thrombosis, a physiological disorder in which pathological clot formation obstructs normal blood flow. Fewer studies have focused on extravascular clotting where blood leaks out of the vessel from a hole; this scenario could represent the normal hemostatic response where clots form to prevent blood leakage but the blood also retains fluidity in the main blood vessel.…”

“…Our model was also extended by others to include fibrin formation and was then compared with microfluidic experiments to understand how the growth and structure of clots that form under flow vary with initial stimulus. 4,5 Most computational models of platelet aggregation, including our previous work, were used to study intravascular clot formation, where there is no leakage of blood from the vessel [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] ; this scenario models thrombosis, a physiological disorder in which pathological clot formation obstructs normal blood flow. Fewer studies have focused on extravascular clotting where blood leaks out of the vessel from a hole; this scenario could represent the normal hemostatic response where clots form to prevent blood leakage but the blood also retains fluidity in the main blood vessel.…”

A mathematical model to quantify the effects of platelet count, shear rate, and injury size on the initiation of blood coagulation under venous flow conditions

“…Another approach consists in the modelling of the effects of the clot on the viscoelastic properties of blood flow [ 23 ]. In general, the models describing the formation of venous thrombi focus on the distribution of clotting factors in plasma while those studying the development of arterial white thrombi are primarily interested by the dynamics of platelets activation and aggregation [ 24 ]. Although mathematical modelling provides an important tool for the qualitative understanding of the underlying mechanisms behind thrombus growth, it is difficult to properly use it to quantify the effects of these mechanisms.…”