Computational analysis on the mechanical interaction between a thrombus and red blood cells: Possible causes of membrane damage of red blood cells at microvessels

Previous studies investigating thrombus formation have not focused on the physical interaction between red blood cells (RBCs) and thrombus, although they have been speculated that some pathological conditions such as microangiopathic hemolytic anemia (MAHA) stem from interactions between RBCs and thrombi. In this study, we investigated the mechanical influence of RBCs on primary thrombi during hemostasis. We also explored the mechanics and aggravating factors of intravascular hemolysis. Computer simulations of primary thrombogenesis in the presence and the absence of RBCs demonstrated that RBCs are unlikely to affect the thrombus height and coverage, although their presence may change microvessel hemodynamics and platelet transportation to the injured wall. Our results suggest that intravascular hemolysis owing to RBC membrane damage would be promoted by three hemodynamic factors: (1) dispersibility of platelet thrombi, because more frequent spatial thrombus formation decreases the time available for an RBC to recover its shape and enforces more severe deformation; (2) platelet thrombus stiffness, because a stiffer thrombus increases the degree of RBC deformation upon collision; and (3) vessel size and hemocyte density, because a smaller vessel diameter and higher hemocyte density decrease the room for RBCs to escape as they come closer to a thrombus, thereby enhancing thrombus-RBC interactions.