Numerically reproducing the process of thrombus formation is highly desired for understanding its mechanism but still remains challenging due to the polydisperse feature of blood components and their multiple biochemical or biomechanical behaviors involved. We numerically implemented a simplified version of the process from the perspective of biomechanics, using a mesoscale particle-based method, smoothed dissipative particle dynamics-immersed boundary method. This version covers the adhesion and aggregation of platelets (PLTs), the deformation and aggregation of red blood cells (RBCs), and the interaction between PLTs and RBCs, as well as the blockage of microvessels. Four critical factors that can affect thrombus formation were investigated: the velocity of blood flow, the adhesive ability of PLTs, the interaction strength between PLTs and RBCs, and the deformability of RBCs. Increasing the velocity of blood flow was found to be the most effective way to reduce the microvessel blockage, and reducing the adhesive ability of PLTs is also a direct and efficient way. However, decreasing the interaction strength between PLTs and RBCs sometimes does not alleviate thrombus formation, and similarly, 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.