Thrombus formation in flowing blood is a complex time- and space-dependent process ofcell adhesion and fibrin gel formation controlled by huge intricate networks ofbiochemical reactions. This combination of complex biochemistry, non-Newtonianhydrodynamics, and transport processes makes thrombosis difficult to understand. That iswhy numerous attempts to use mathematical modeling for this purpose were undertaken duringthe last decade. In particular, recent years witnessed something of a transition from the“systems biology” to the “systems pharmacology/systems medicine” stage: computationalmodeling is being increasingly applied to practical problems such as drug development,investigation of particular events underlying disease, analysis of the mechanism(s) ofdrug’s action, determining an optimal dosing protocols, etc. Here we review recentadvances and challenges in our understanding of thrombus formation.

We perform a sensitivity analysis for a thus far unstudied mathematical model for theformation, growth and lysis of clots in vitro. The sensitivity analysis procedure uses anensemble standard deviation for species concentrations, and is equivalent to a variancedecomposition procedure also available in the literature. Our analysis shows that fibrinproduction is most sensitive to the rate constant governing activation of prothrombin tothrombin. Further, the time-averaged sum of all species’ concentrations is most sensitiveto the rate constants governing the inactivation of VIIIa (intrinsic as well as by APC).We therefore conclude that the rate constants for VIIIa inactivation affect the model thegreatest: this conclusion must be experimentally verified to determine if such is indeedthe case for hemostasis.

This paper presents numerical results based on a macroscopic blood coagulation modelcoupled with a non-linear viscoelastic model for blood flow. The system of governingequations is solved using a central finite-volume scheme for space discretization and anexplicit Runge-Kutta time-integration. An artificial compressibility method is used toresolve pressure and a non-linear TVD filter is applied for stabilization. A simple testcase of flowing blood over a clotting surface in a straight 3D vessel is solved. This workpresents a significant extension of the previous studies [10] and [9].

A stenosis is the narrowing of the artery, this narrowing is usually the result of theformation of an atheromatous plaque infiltrating gradually the artery wall, forming a bumpin the ductus arteriosus. This arterial lesion falls within the general context ofatherosclerotic arterial disease that can affect the carotid arteries, but also thearteries of the heart (coronary), arteries of the legs (PAD), the renal arteries... It cancause a stroke (hemiplegia, transient paralysis of a limb, speech disorder, sailing beforethe eye). In this paper we study the blood-plaque and blood-wall interactions using afluid-structure interaction model. We first propose a 2D analytical study of thegeneralized Navier-Stokes equations to prove the existence of a weak solution forincompressible non-Newtonian fluids with non standard boundary conditions. Then, coupled,based on the results of the theoretical study approach is given. And to form a realisticmodel, with high accuracy, additional conditions due to fluid-structure coupling areproposed on the border undergoing inetraction. This coupled model includes (a) a fluidmodel, where blood is modeled as an incompressible non-Newtonian viscous fluid, (b) asolid model, where the arterial wall and atherosclerotic plaque will be treated as nonlinear hyperelastic solids, and (c) a fluid-structure interaction (FSI) model whereinteractions between the fluid (blood) and structures (the arterial wall and atheromatousplaque) are conducted by an Arbitrary Lagrangian Eulerian (ALE) method that allowsaccurate fluid-structure coupling.

Properties of blood cells and their interaction determine their distribution in flow. Itis observed experimentally that erythrocytes migrate to the flow axis, platelets to thevessel wall, and leucocytes roll along the vessel wall. In this work, a three-dimensionalmodel based on Dissipative Particle Dynamics method and a new hybrid (discrete-continuous)model for blood cells is used to study the interaction of erythrocytes with platelets andleucocytes in flow. Erythrocytes are modelled as elastic highly deformable membranes,while platelets and leucocytes as elastic membranes with their shape close to a sphere.Separation of erythrocytes and platelets in flow is shown for different values ofhematocrit. Erythrocyte and platelet distributions are in a good qualitative agreementwith the existing experimental results. Migration of leucocyte to the vessel wall and itsrolling along the wall is observed.

In this work we propose a method for analysis of postsurgical haemodynamics after femoralartery treatment of occlusive vascular disease. Patient specific reconstruction algorithmof 1D core network based on MRI data is proposed as a tool for such analysis. Along withpresurgical ultrasound data fitting it provides effective personalizing predictive methodthat is validated with clinical observations.

We present a fully automatic approach to recover boundary conditions and locations of thevessel wall, given a crude initial guess and some velocity cross-sections, which can becorrupted by noise. This paper contributes to the body of work regarding patient-specificnumerical simulations of blood flow, where the computational domain and boundaryconditions have an implicit uncertainty and error, that derives from acquiring andprocessing clinical data in the form of medical images. The tools described in this paperfit well in the current approach of performing patient-specific simulations, where areasonable segmentation of the medical images is used to form the computational domain,and boundary conditions are obtained as velocity cross-sections from phase-contrastmagnetic resonance imaging. The only additional requirement in the proposed methods is toobtain additional velocity cross-section measurements throughout the domain. The toolsdeveloped around optimal control theory, would then minimize a user defined cost functionto fit the observations, while solving the incompressible Navier-Stokes equations.Examples include two-dimensional idealized geometries and an anatomically realisticsaccular geometry description.

A traceless variant of the Johnson-Segalman viscoelastic model is presented and appliedto blood flow simulations. The viscoelastic extra stress tensor is decomposed into itstraceless (deviatoric) and spherical parts, leading to a reformulation of the classicalJohnson-Segalman model. The equivalence of the two models is established comparing modelpredictions for simple test cases. The new model is validated using several 2D benchmarkproblems, designed to reproduce difficulties that arise in the simulation of blood flow inblood vessels or medical devices. The structure and behaviour of the new model arediscussed and the future use of the new model in envisioned, both on the theoretical andnumerical perspectives.