A constitutive model for developing blood clots with various compositions and their nonlinear viscoelastic behavior (original) (raw)
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Molecules
(1) Background: Together with treatment protocols, viscoelastic tests are widely used for patient care. Measuring at broader ranges of deformation than currently done will add information on a clot's mechanical phenotype because fibrin networks follow different stretching regimes, and blood flow compels clots into a dynamic non-linear response. (2) Methods: To characterize the influence of platelets on the network level, a stress amplitude sweep test (LAOStress) was applied to clots from native plasma with five platelet concentrations. Five species were used to validate the protocol (human, cow, pig, rat, horse). By Lissajous plots the oscillation cycle for each stress level was analyzed. (3) Results: Cyclic stress loading generates a characteristic strain response that scales with the platelet quantity at low stress, and that is independent from the platelet count at high shear stress. This general behavior is valid in the animal models except cow. Here, the specific fibrinogen chemistry induces a stiffer network and a variant high stress response. (4) Conclusions: The protocol provides several thresholds to connect the softening and stiffening behavior of clots with the applied shear stress. This points to the reversible part of deformation, and thus opens a new route to describe a blood clot's phenotype.
Journal of the Royal Society, Interface, 2017
Thromboembolism, one of the leading causes of morbidity and mortality worldwide, is characterized by formation of obstructive intravascular clots (thrombi) and their mechanical breakage (embolization). A novel two-dimensional multi-phase computational model is introduced that describes active interactions between the main components of the clot, including platelets and fibrin, to study the impact of various physiologically relevant blood shear flow conditions on deformation and embolization of a partially obstructive clot with variable permeability. Simulations provide new insights into mechanisms underlying clot stability and embolization that cannot be studied experimentally at this time. In particular, model simulations, calibrated using experimental intravital imaging of an established arteriolar clot, show that flow-induced changes in size, shape and internal structure of the clot are largely determined by two shear-dependent mechanisms: reversible attachment of platelets to th...
Clinical Hemorheology and Microcirculation, 2015
Incipient clot formation in whole blood and fibrin gels was studied by the rheometric techniques of controlled stress parallel superposition (CSPS) and small amplitude oscillatory shear (SAOS). The effects of unidirectional shear stress on incipient clot microstructure, formation kinetics and elasticity are reported in terms of the fractal dimension (d f) of the fibrin network, the gel network formation time (T GP) and the shear elastic modulus, respectively. The results of this first haemorheological application of CSPS reveal the marked sensitivity of incipient clot microstructure to physiologically relevant levels of shear stress, these being an order of magnitude lower than have previously been studied by SAOS. CSPS tests revealed that exposure of forming clots to increasing levels of shear stress produces a corresponding elevation in d f , consistent with the formation of tighter, more compact clot microstructures under unidirectional flow. A corresponding increase in shear elasticity was recorded. The scaling relationship established between shear elasticity and d f for fibrin clots and whole blood confirms the fibrin network as the dominant microstructural component of the incipient clot in terms of its response to imposed stress. Supplementary studies of fibrin clot formation by rheometry and microscopy revealed the substantial additional network mass required to increase d f and provide evidence to support the hypothesis that microstructural changes in blood clotted under unidirectional shear may be attributed to flow enhanced thrombin generation and activation. CSPS also identified a threshold value of unidirectional shear stress above which no incipient clot formation could be detected. CSPS was shown to be a valuable haemorheological tool for the study of the effects of physiological and pathological levels of shear on clot properties.
2007
Modeling by means of employing the generalized and modified Maxwell-Gurevich- Rabinovich (MGR) model, presented in this study, is based on our experimental data found using Low Shear 30 sinus Contraves rotational viscometer at different regimes of blood shear flow: steady and unsteady - transient and sinusoidal flow. The rheological behaviour of the human blood is characterized by pseudoplasticity, thixotropy and viscoelasticity. According to the MGR model the full strain rate at shear is a superposition of the elastic strain rate, the residual strain rate and the high elastic strain rate. The elastic modulus of shear G , the initial coefficient of viscosity 0 K and the logarithmic modulus of the strain rate m link ∏ ® x J for a detailed description of the observed relationships some modifications of the MGR model are proposed. The parameters of the proposed models are found from experimental data and used for blood micro structuring analysis.
Interplay of Platelet Contractility and Elasticity of Fibrin/Erythrocytes in Blood Clot Retraction
Biophysical journal, 2017
Blood clot contraction (retraction) is driven by platelet-generated forces propagated by the fibrin network and results in clot shrinkage and deformation of erythrocytes. To elucidate the mechanical nature of this process, we developed a model that combines an active contractile motor element with passive viscoelastic elements. Despite its importance for thrombosis and wound healing, clot contraction is poorly understood. This model predicts how clot contraction occurs due to active contractile platelets interacting with a viscoelastic material, rather than to the poroelastic nature of fibrin, and explains the observed dynamics of clot size, ultrastructure, and measured forces. Mechanically passive erythrocytes and fibrin are present in series and parallel to active contractile cells. This mechanical interplay induces compressive and tensile resistance, resulting in increased contractile force and a reduced extent of contraction in the presence of erythrocytes. This experimentally v...
A Model for the Formation and Lysis of Blood Clots
Pathophysiology of Haemostasis and Thrombosis, 2005
Both biochemical and mechanical factors have to be taken into account if a meaningful model for the formation, growth, and lysis of clots in flowing blood is to be developed. Most models that are currently in use neglect one or the other of these factors. We have previously reported a model [J Theoret Med 2003;5:183–218] that we believe is a step in this direction, incorporating many of the crucial biochemical and rheological factors that play a role in the formation, growth, and lysis of clots. While this model takes into account the extrinsic pathway of coagulation, it largely ignores the intrinsic pathway. Here, we discuss some of the general issues with respect to mathematical modeling of thrombus formation and lysis, as well as specific aspects of the model that we have developed.
Materials
This work focuses on the advanced modeling of the thixotropic nature of blood, coupled with an elasto-visco-plastic formulation by invoking a consistent and validated model for TEVP materials. The proposed model has been verified for the adequate description of the rheological behavior of suspensions, introducing a scalar variable that describes dynamically the level of internal microstructure of rouleaux at any instance, capturing accurately the aggregation and disaggregation mechanisms of the RBCs. Also, a non-linear fitting is adopted for the definition of the model’s parameters on limited available experimental data of steady and transient rheometric flows of blood samples. We present the predictability of the new model in various steady and transient rheometric flows, including startup shear, rectangular shear steps, shear cessation, triangular shear steps and LAOS tests. Our model provides predictions for the elasto-thixotropic mechanism in startup shear flows, demonstrating a...
Fluid Mechanics of Blood Clot Formation
Annual Review of Fluid Mechanics, 2015
Intravascular blood clots form in an environment in which hydrodynamic forces dominate and in which fluid-mediated transport is the primary means of moving material. The clotting system has evolved to exploit fluid dynamic mechanisms and to overcome fluid dynamic challenges to ensure that clots that preserve vascular integrity can form over the wide range of flow conditions found in the circulation. Fluid-mediated interactions between the many large deformable red blood cells and the few small rigid platelets lead to high platelet concentrations near vessel walls where platelets contribute to clotting. Receptor-ligand pairs with diverse kinetic and mechanical characteristics work synergistically to arrest rapidly flowing cells on an injured vessel. Variations in hydrodynamic stresses switch on and off the function of key clotting polymers. Protein transport to, from, and within a developing clot determines whether and how fast it grows. We review ongoing experimental and modeling re...
A constitutive model for the time-dependent, nonlinear stress response of fibrin networks
Biomechanics and Modeling in Mechanobiology, 2015
Blood clot formation is important to prevent blood loss in case of a vascular injury but disastrous when it occludes the vessel. As the mechanical properties of the clot are reported to be related to many diseases, it is important to have a good understanding of their characteristics. In this study, a constitutive model is presented that describes the nonlinear viscoelastic properties of the fibrin network, the main structural component of blood clots. The model is developed using results of experiments in which the fibrin network is subjected to a large amplitude oscillatory shear (LAOS) deformation. The results show three dominating nonlinear features: softening over multiple deformation cycles, strain stiffening and increasing viscous dissipation during a deformation cycle. These features are incorporated in a constitutive model based on the Kelvin-Voigt model. A network state parameter is introduced that takes into account the influence of the deformation history of the network. Furthermore, in the period following the LAOS deformation, the stiffness of the networks increases which is also incorporated in the model. The influence of cross-links created by factor XIII is investigated by comparing fibrin networks that have polymerized for 1 and 2 h. A sensitivity analysis provides insights into the influence of the eight fit parameters. The model developed is able to describe the rich, time-dependent, nonlinear behavior of the fibrin network. The model is relatively simple which makes it suitable for computational sim-ulations of blood clot formation and is general enough to be used for other materials showing similar behavior.
Blood Coagulation Simulations using a Viscoelastic Model
Mathematical Modelling of Natural Phenomena, 2014
This paper presents numerical results based on a macroscopic blood coagulation model coupled with a non-linear viscoelastic model for blood flow. The system of governing equations is solved using a central finite-volume scheme for space discretization and an explicit Runge-Kutta time-integration. An artificial compressibility method is used to resolve pressure and a non-linear TVD filter is applied for stabilization. A simple test case of flowing blood over a clotting surface in a straight 3D vessel is solved. This work presents a significant extension of the previous studies [10] and [9].