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XXVIII conference

Mathematical modeling of shear-induced platelet activation in large human vessels

Salikhova T.Y., Pushin D.M., Guria G.Th.

National Research Center for Hematology, Russia, 125167, Moscow, Novy Zykovsky proezd, 4; Moscow Institute of Physics and Technology, Russia, 141701, Moscow Region, Dolgoprudny, Institutskiy per., 9

1 pp. (accepted)

High shear stresses in intense blood flow can trigger platelet activation, leading to the development of severe complications (heart attacks, strokes). The analysis of shear-induced platelet activation risks requires the correct accounting of the hemodynamic features in the investigated large vessel [1]. The aim of this work is to develop a mathematical approach for the estimation of shear-induced platelet activation risks in large human vessels.

The approach is based on the condition of platelet activation obtained in the article [2]. According to this condition, platelet activation is a threshold process, and the threshold value depends on the length of von Willebrand factor (VWF) plasma macromolecules. According to the proposed approach, the risk of platelet activation is analyzed in two stages. At the first stage, the distribution of the shear stress absolute value is calculated. At the second stage, the activated platelets are calculated. The activated platelets ratio averaged over the cardiac cycle at the outlet of the vessel is used as a measure of the shear-induced platelet activation risk.

The proposed approach was used to analyze the risks of platelet activation in the aorta. Its geometry was reconstructed based on the data of magnetic resonance imaging. The dependence of the degree of platelet activation on the multimeric size of VWF molecules and flow through the aorta was built. It was found that VWF molecules with a length less than the critical are unable to induce platelet activation.

The length of VWF molecules in blood plasma can be directly changed towards long molecules (desmopressin) and towards short molecules (ADAMTS-13). The developed approach will make it possible to estimate the influence of these therapeutic effects on the degree of shear-induced platelet activation.

The work was supported by grant No 19-11-00260 of Russian Science Foundation.

References

1. Pushin D.M., Salikhova T.Y., Zlobina K.E., Guria G.Th. Platelet activation via dynamic conformational changes of von Willebrand factor under shear // PLOS ONE Vol. 15, 2020. Pp. 1‑17.

2. Zlobina K.E., Guria G.Th. Platelet activation risk index as a prognostic thrombosis indicator // Scientific Reports Vol. 6, 2016. Pp. 1-6.



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