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

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.

Patient-Specific Modelling of Blood Coagulation

“…Kinetics curves in thrombin generation tests are described by kinetic ODE models (Chelle et al 2018;Dunster and King 2017;Hoffman et al 2005;Mann et al 2003) (see also Belyaev et al 2018;Panfilov 2019;Tokarev et al 2019 for a more complete literature review). Clot growth in a quiescent plasma is investigated with reaction-diffusion equations (Guria and Guria 2015;Pogorelova and Lobanov 2014;Zarnitsina et al 2001), clot growth in blood flow is studied by various continuous models (Belyaev et al 2015;Bouchnita et al 2020;Sequeira et al 2011;Bodnar and Sequeira 2008;Sequeira and Bodnar 2014), particle Fig. 12 Joint action of heparin and warfarin on three virtual patients.…”

“… 2015 ; Bouchnita et al. 2020 ; Sequeira et al. 2011 ; Bodnar and Sequeira 2008 ; Sequeira and Bodnar 2014 ), particle and hybrid models (Tosenberger et al.…”

“…Complete vessel occlusion for a dense clot is impossible in this case. If the pressure difference is given and not the total flow rate, then flow velocity above the clot can either increase or decrease depending on its width (Bouchnita et al 2017a(Bouchnita et al , 2020. Decelerating flow velocity promotes further clot growth which can lead to the complete vessel occlusion.…”

Platelet dysfunction after trauma: From mechanisms to targeted treatment

“…15 Platelet counts drop during intensive care unit (ICU) stay, but rise 72-h post injury, resulting in a reactive thrombocytosis, 53 which is correlated with increased cloth strength. 63,64 This hypercoagulable profile is associated with (venous) thromboembolic events (VTE). 63,65 Post-injury arterial thrombosis is less frequently diagnosed and is associated with older age, indicating different underlying mechanisms.…”

“…Shock, injury severity, TBI and early platelet dysfunction are all associated with these late complications 15 . Platelet counts drop during intensive care unit (ICU) stay, but rise 72‐h post injury, resulting in a reactive thrombocytosis, 53 which is correlated with increased cloth strength 63,64 . This hypercoagulable profile is associated with (venous) thromboembolic events (VTE) 63,65 .…”