ИСТИНА

Background: The regulation of thrombus growth and stability is crucial for normal hemostasis, though the mechanisms involved in limitation of thrombus growth are still a matter of controversy. It is generally accepted that ferric chloride–induced thrombi are normally occlusive while laser and micropuncture-induced thrombi do not significantly reduce the blood flow. Recent in vivo studies of laser-induced thrombosis in mice revealed core-and-shell architecture of the forming hemostatic thrombus. Dynamics of thrombus shell formed by reversibly adherent discoid platelets determines its size and shape during initial stages of thrombus formation. Aims: This study aimed at computational analysis of impact that vessel injury size makes on dynamics of reversibly adherent platelets. We proposed that damage length might be crucial parameter determining the outcome of the vessel injury. Methods: We developed a 2d computational model of platelet plug formation under high-shear conditions corresponding to arterioles and venules. Platelets were considered as semi-rigid discoid particles placed in Newtonian fluid described with Navier-Stokes equations. Constant pressure drop boundary conditions were implemented in order to resolve vessel occlusion. Using quasi-steady flow approximation made it possible to study simulations corresponding to physiologically relevant timescales of dozens of seconds. Results: In case of small-scale endothelium damage of several microns our model demonstrates unstable behavior of thrombus shell which is consistent with recent in vivo observations. Larger-scale damage of 40 microns results in larger stable thrombus leading to full occlusion of 35 μm – wide vessel. Conclusion: Damage length along the blood vessel might be important factor determining the size and stability of the platelet plug formed under high shear conditions. These results might explain the differences of vessel injury outcomes observed for various thrombosis models.