Modelling of thrombus growth in flow with a DPD-PDE method.

Hemostatic plug covering the injury site (or a thrombus in the pathological case) is formed due to the complex interaction of aggregating platelets with biochemical reactions in plasma that participate in blood coagulation. The mechanisms that control clot growth and which lead to growth arrest are not yet completely understood. We model them with numerical simulations based on a hybrid DPD-PDE model. Dissipative particle dynamics (DPD) is used to model plasma flow with platelets while fibrin concentration is described by a simplified reaction-diffusion-advection equation. The model takes into account consecutive stages of clot growth. First, a platelet is weakly connected to the clot and after some time this connection becomes stronger due to other surface receptors involved in platelet adhesion. At the same time, the fibrin mesh is formed inside the clot. This becomes possible because flow does not penetrate the clot and cannot wash out the reactants participating in blood coagulation. Platelets covered by the fibrin mesh cannot attach new platelets. Modelling shows that the growth of a hemostatic plug can stop as a result of its exterior part being removed by the flow thus exposing its non-adhesive core to the flow.

[1]  P Mangin,et al.  A revised model of platelet aggregation. , 2000, The Journal of clinical investigation.

[2]  Zhiliang Xu,et al.  A multiscale model of thrombus development , 2008, Journal of The Royal Society Interface.

[3]  G. Panasenko,et al.  Continuous mathematical model of platelet thrombus formation in blood flow , 2012 .

[4]  Patrick B. Warren,et al.  Dissipative particle dynamics , 1998 .

[5]  K. Rajagopal,et al.  A Model for the Formation and Lysis of Blood Clots , 2006, Pathophysiology of Haemostasis and Thrombosis.

[6]  Hong Zhao,et al.  Shear-induced particle migration and margination in a cellular suspension , 2012 .

[7]  N. Filipovic,et al.  Modelling thrombosis using dissipative particle dynamics method , 2008, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[8]  U. Windberger,et al.  Whole Blood Viscosity, Plasma Viscosity and Erythrocyte Aggregation in Nine Mammalian Species: Reference Values and Comparison of Data , 2003, Experimental physiology.

[9]  Zhiliang Xu,et al.  Two-photon intravital imaging of thrombus development. , 2010, Journal of biomedical optics.

[10]  A wave propagation algorithm for viscoelastic fluids with spatially and temporally varying properties , 2008 .

[11]  F. Ataullakhanov,et al.  Platelet transport and adhesion in shear blood flow: the role of erythrocytes , 2012 .

[12]  Aaron L Fogelson,et al.  Fibrin gel formation in a shear flow. , 2007, Mathematical medicine and biology : a journal of the IMA.

[13]  L. McIntire,et al.  Adhesion of platelets to surface-bound fibrinogen under flow , 1996 .

[14]  Aleksandar M. Spasic,et al.  Finely Dispersed Particles : Micro-, Nano-, and Atto-Engineering , 2005 .

[15]  B. Furie,et al.  Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse , 2002, Nature Medicine.

[16]  J. Weisel Enigmas of Blood Clot Elasticity , 2008, Science.

[17]  Vitaly Volpert,et al.  Particle Dynamics Methods of Blood Flow Simulations , 2011 .

[18]  Shaun P Jackson,et al.  The growing complexity of platelet aggregation. , 2007, Blood.

[19]  P. B. Warren,et al.  DISSIPATIVE PARTICLE DYNAMICS : BRIDGING THE GAP BETWEEN ATOMISTIC AND MESOSCOPIC SIMULATION , 1997 .

[20]  F. Ataullakhanov,et al.  Spatiotemporal dynamics of fibrin formation and spreading of active thrombin entering non-recalcified plasma by diffusion. , 2000, Biochimica et biophysica acta.

[21]  Jerrold E. Marsden,et al.  Study of blood flow impact on growth of thrombi using a multiscale model , 2009 .

[22]  Dennis E. Discher,et al.  Multiscale Mechanics of Fibrin Polymer: Gel Stretching with Protein Unfolding and Loss of Water , 2009, Science.

[23]  Zhiliang Xu,et al.  A multiscale model of venous thrombus formation with surface-mediated control of blood coagulation cascade. , 2010, Biophysical journal.

[24]  P. Richardson,et al.  Effect of red blood cells on platelet aggregation , 2009, IEEE Engineering in Medicine and Biology Magazine.

[25]  M. Frojmovic,et al.  Dynamics of platelet glycoprotein IIb-IIIa receptor expression and fibrinogen binding. I. Quantal activation of platelet subpopulations varies with adenosine diphosphate concentration. , 1994, Biophysical journal.

[26]  T. Bodnár,et al.  Numerical Simulation of the Coagulation Dynamics of Blood , 2008 .

[27]  A. Fogelson Cell-based Models of Blood Clotting , 2007 .

[28]  A. Wolberg,et al.  Procoagulant activity induced by vascular injury determines contribution of elevated factor VIII to thrombosis and thrombus stability in mice. , 2011, Blood.

[29]  G. Karniadakis,et al.  A new method to impose no-slip boundary conditions in dissipative particle dynamics , 2005 .

[30]  S. Jackson,et al.  Dynamics of platelet thrombus formation , 2009, Journal of thrombosis and haemostasis : JTH.

[31]  F. Ataullakhanov,et al.  Platelet adhesion from shear blood flow is controlled by near-wall rebounding collisions with erythrocytes. , 2011, Biophysical journal.

[32]  Alexey M. Shibeko,et al.  Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa , 2010, BMC Systems Biology.

[33]  C. Mao,et al.  Platelet-fibrin interaction in the suspension and under flow conditions. , 1990, Advances in experimental medicine and biology.

[34]  G. Panasenko,et al.  Finite platelet size could be responsible for platelet margination effect. , 2011, Biophysical journal.

[35]  George E. Karniadakis,et al.  Velocity limit in DPD simulations of wall-bounded flows , 2008, J. Comput. Phys..

[36]  Christopher R. Sweet,et al.  Modelling platelet–blood flow interaction using the subcellular element Langevin method , 2011, Journal of The Royal Society Interface.

[37]  Aaron L. Fogelson,et al.  Immersed-boundary-type models of intravascular platelet aggregation☆ , 2008 .

[38]  Dmitry A. Fedosov,et al.  Multiscale Modeling of Blood Flow and Soft Matter , 2010 .

[39]  Cameron W. Harvey,et al.  Multiscale model of fibrin accumulation on the blood clot surface and platelet dynamics. , 2012, Methods in cell biology.

[40]  Aaron L. Fogelson,et al.  Analysis of mechanisms for platelet near-wall excess under arterial blood flow conditions , 2011, Journal of Fluid Mechanics.

[41]  Mikhail A Panteleev,et al.  Task-oriented modular decomposition of biological networks: trigger mechanism in blood coagulation. , 2010, Biophysical journal.

[42]  J. S. Lin,et al.  Direct observation of platelet adhesion to fibrinogen- and fibrin-coated surfaces. , 1991, The American journal of physiology.

[43]  K R Rajagopal,et al.  A model for the formation, growth, and lysis of clots in quiescent plasma. A comparison between the effects of antithrombin III deficiency and protein C deficiency. , 2008, Journal of theoretical biology.

[44]  G. Karniadakis,et al.  Blood flow velocity effects and role of activation delay time on growth and form of platelet thrombi , 2006, Proceedings of the National Academy of Sciences.

[45]  Chiu Yl,et al.  Platelet deposition onto fibrin-coated surfaces under flow conditions. , 1988 .

[46]  J. Banavar,et al.  Computer Simulation of Liquids , 1988 .

[47]  N. Bessonov,et al.  Numerical simulation of blood flows with non-uniform distribution of erythrocytes and platelets , 2013 .

[48]  C. Jen,et al.  Morphological study of platelet adhesion dynamics under whole blood flow conditions. , 1992, Platelets.

[49]  Mikhail A Panteleev,et al.  Spatial propagation and localization of blood coagulation are regulated by intrinsic and protein C pathways, respectively. , 2006, Biophysical journal.

[50]  Shigeo Wada,et al.  A particle method for blood flow simulation: application to flowing red blood cells and platelets , 2006 .