PB0001 - Force balance ratio is a robust predictor of arterial thrombus embolization

Background: Thrombus formation on a damaged vessel wall can lead to the formation of a stable occlusive/subocclusive clot or unstable embolizing thrombus. Both outcomes can cause significant health damage. The mechanisms that regulate maximum thrombus size, its stability and embolization in both micro- and macrocirculation are poorly understood.

Aims: To investigate the impact of flow and intrathrombus forces on the stability of homogeneous and heterogeneous platelet aggregates in a wide range of thrombus geometries, critical interplatelet forces, vessel diameters and hydrodynamic conditions we took advantage of the recently developed in silico models.

Methods: To perform analysis of thrombus stability/embolization in arterioles we used a previously developed particle-based 2D model with single-platelet resolution. Its results and predictions were further extended to a 3D case and the large spatial scales of arteries using novel particle-based and continuous 3D models.

Results: We found a robust quantitative parameter, termed a ‘force balance ratio’, which depends on the bulk hydrodynamic force acting on a thrombus, the area of contact between thrombus and the vessel wall, and the critical interplatelet forces. This parameter predicts whether a homogeneous thrombus (or the shell of a heterogeneous thrombus) with given critical interplatelet forces will embolize under given hydrodynamic conditions (Figure 1). Using a force balance ratio, we showed that longer platelet aggregates are more stable, and that thrombus formed on top of the plaque in case of moderate stenosis are less stable than thrombi formed on the plaque producing severe stenosis (Figure 2).

Conclusion(s): Taken together, our results give the new insights into the interplay between critical interplatelet forces, local hydrodynamics and overall thrombus stability against the flow. Our results predict that thrombi growing at severe stenosis are more stable (hence, potentially more life-threatening), than thrombi formed at the moderate stenosis conditions.

This work was supported by the Russian Science Foundation grant 22-24-01028.