ИСТИНА

Introduction Von Willebrand factor (VWF) plays a central role in transmitting the effect of blood flow shear stress to intracellular platelet activation pathways [1]. This mechanism of platelet activation takes place exclusively under high shear flow. Shear-induced platelet activation in some cases is accompanied by severe intravascular thrombotic complications [2]. Development of mathematical models allowing to evaluate the platelet activation intensity in high shear flow is of considerable interest. The goal of this study is to develop a mathematical model of shear-induced platelet activation in high intravascular blood flow. Methods The platelet activation model presented here includes two groups of equations: equations of motion that govern the blood flow and a set of coupled convection-diffusion-reaction equations that determine transport and inter-conversion of chemical species (vWF molecules with different degree of multimerization, non-activated and activated platelets). The kinetics of platelet transition to the activated state is assumed to be dependent on the concentration of non-activated platelets and unwinding vWF molecules. The degree of vWF unwinding is considered to depend on the shear stress in accordance with the work [3]. The governing parameters in the model are the Reynolds number, flow geometry and characteristics of vWF size distribution. Results The model was applied to the investigation of platelet activation in hemodialysis arteriovenous fistula and FDA Centrifugal Blood Pump [4]. The ratio of the activated platelets number at the domain exit to the total platelets number at the entrance was used as a measure characterizing the intensity of platelet activation. Numerical analysis revealed that an increase in the proportion of activated platelets is observed both with increasing blood flow intensity and with increasing content of high molecular weight vWF. Conclusions The model of shear-induced platelet activation allowing to quantify platelet activation intensity under high shear flow in objects with complex spatial geometry was described. This model provided an opportunity to analyze the influence of chemical and hemodynamic stimuli on kinetics of thrombosis process. As a result, the opportunity for rational interpretation of a number of clinical observations was opened [5]. Acknowledgements References 1. Ruggeri Z. M. et al., (2006). Blood, 108(6) p1903 2. Slepian M. J. et al., (2017). J Biomech, 50 p20 3. Zlobina K.E. et al., (2016). Sci Rep, 6(30508) p1 4. Computational Fluid Dynamics: An FDA Critical Path Initiative, https://fdacfd.nci.nih.gov/ 5. Casa L. D.C. et al., (2015). J Vasc Surg, 61(4) p1068