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

PLoS One. 2020 Jul 29;15(7):e0235392. doi: 10.1371/journal.pone.0235392. eCollection 2020.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation / physiology*
  • Blood Coagulation Tests
  • Blood Platelets / metabolism
  • Blood Platelets / physiology*
  • Fibrin / metabolism
  • Humans
  • Models, Theoretical*
  • Platelet Aggregation / physiology
  • Platelet Count / methods*
  • Regional Blood Flow / physiology
  • Shear Strength / physiology
  • Thrombin / metabolism
  • Thromboplastin / metabolism
  • Thrombosis / metabolism
  • Thrombosis / physiopathology
  • Veins / metabolism
  • Veins / physiology

Substances

  • Fibrin
  • Thromboplastin
  • Thrombin

Grants and funding

K. Terekhov was supported by RFBR grant 18-31-20048. Yu. Vassilevski was supported by the world-class research center "Moscow Center for Fundamental and Applied Mathematics" (agreement with the Ministry of Education and Science of the Russian Federation No. 075-15-2019-1624). V. Volpert was supported by the “RUDN University Program 5-100.” The development of the 3D numerical model of thrombus growth under venous flow conditions was supported by Russian Science Foundation grant 14-31-00024. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.