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

Platelets upregulate the generation of thrombin and reinforce the fibrin clot which increases the incidence risk of venous thromboembolism (VTE). However, the role of platelets in the pathogenesis of venous cardiovascular diseases remains hard to quantify. An experimentally validated model of thrombin generation dynamics is formulated. The model predicts that a high platelet count increases the peak value of generated thrombin as well as the endogenous thrombin potential (ETP) as reported in experimental data. To investigate the effects of platelets density, shear rate, and wound size on the initiation of blood coagulation, we calibrate a previously developed model of venous thrombus formation and implement it in 3D using a novel cell-centered finite-volume solver. We conduct numerical simulations to reproduce in vitro experiments of blood coagulation in microfluidic capillaries. Then, we derive a reduced one-equation model of thrombin distribution from the previous model under simplifying hypotheses and we use it to determine the conditions of clotting initiation on the platelet count, the shear rate, and the plasma composition. The initiation of clotting also exhibits a threshold response to the size of the wounded region in good agreement with the reported experimental findings. © 2020 Bouchnita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bouchnita A.1 , Terekhov K.2 , Nony P.3 , Vassilevski Y.2, 4, 5 , Volpert V. 2, 6, 7, 8
Public Library of Science
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7 July
  • 1 Ecole Centrale Casablanca, Casablanca, Morocco
  • 2 Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow, Russian Federation
  • 3 Services de Pharmacologie Clinique, Hospices Civils de Lyon, Lyon, France
  • 4 Sechenov University, Moscow, Russian Federation
  • 5 Moscow Institute of Physics and Technology, Dolgoprudny, Russian Federation
  • 6 Institut Camille Jordan, Université Lyon 1, Villeurbanne, France
  • 7 INRIA team Dracula, INRIA Lyon La Doua, Villeurbanne, France
  • 8 Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation
prothrombin; thrombin; fibrin; thrombin; thromboplastin; Article; blood clotting; blood clotting parameters; blood flow; controlled study; diffusion coefficient; dynamics; endogenous thrombin potential; hydraulic permeability; in vitro study; limit of quantitation; mathematical model; microfluidics; platelet count; shear rate; validation process; vein blood flow; viscosity; blood clotting; blood clotting test; human; metabolism; pathophysiology; physiology; platelet count; procedures; shear strength; theoretical model; thrombocyte; thrombocyte aggregation; thrombosis; vein; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Fibrin; Humans; Models, Theoretical; Platelet Aggregation; Platelet Count; Regional Blood Flow; Shear Strength; Thrombin; Thromboplastin; Thrombosis; Veins
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