Biomechanics In Thrombus Formation From Hemodynamics Simulations

Thrombotic diseases,such as strokes and ischemic heart diseases,remain the leading causes of death and disability worldwide.Thrombus formation is a complex,dynamic and multistep process,involving biochemical reactions,mechanical stimulation,hemodynamics,and so on.In recent years,there have been increasing interests in the mechanism of thrombosis,in order to well prevent and treat such diseases.However,it is still challenging to recapitulate mechanical microenvironments of thrombosis,either from experimental,numerical or theoretical perspectives.Experimental observations are limited by the reliability of in vivo measurements;numerical modeling is hardly carried out due to the complexity of vascular network and the diversity of cell behaviors;theoretical principles are also difficultly formed for each stages of thrombosis because of unknown molecular mechanism.In the present thesis,we adopt a mesoscopic numerical method,the hybrid method of smooth dissipative particle dynamics and immersed boundary method,to reproduce a simple version of the thrombus formation as real as possible.This version covers the main steps of the thrombus formation,including the adhesion and aggregation of platelets(PLTs),the deformation and aggregation of red blood cells(RBCs),the interaction between PLTs and RBCs,as well as the blockage of microvessel.The mesoscopic method allows us not only to capture the molecular details of PLT adhesion,but also to describe the macro behaviors of a large number of cells.Five simulation cases are performed and four critical factors are examined,including the velocity of blood flow,the adhesive ability of PLTs,the interaction strength between PLTs and RBCs,and the deformability of RBCs.Our investigations mainly showed that increasing the velocity of blood flow is the most effective way to reduce the microvessel blockage,significantly reducing the vessel blockage.Reducing the adhesive ability of PLTs is also a direct and efficient way,which is the main foundation of some anticoagulant and antiplatelet drugs.Increasing the interaction between the RBCs and PLTs may or may not aggravate the vessel blockage.If the blockage has been severe,the strong interaction causes more RBCs to be captured onto the stenosed region by the PLTs,such that the blockage gets worse and worse.However,if the blockage is not severe,the strong interaction enables the RBCs to bring away the PLTs to pass through the stenosis together,such that the PLT adhesion does not happen and the blockage is thus not aggravated.However,increasing the deformability of RBCs does not have a significant improvement for the severely blocked microvessel.These results imply that maintaining high-rate blood flow plays a crucial role in the prevention and treatment of thrombosis,which is even more effective than antiplatelet or anticoagulant drugs.The drugs or treatments concentrating on reducing the PLT-RBC interaction or softening the RBCs may not have a significant effect on the thrombosis.