Blood clot contraction depends on spatial distribution of fibrin, red blood cells and platelets

Whole-blood clot contraction is a mechanically active process in which fibrin, platelets, red blood cells (RBCs), and fluid reorganize to determine the final compacted state of a clot. Although clot contraction is often associated with platelet activity, experiments and simulations show that RBCs and fibrin can redistribute during contraction, depending on clot size, shape and other parameters. Here, we propose a physics-based three-dimensional equilibrium continuum model for whole-blood clot contraction that combines nonlinear fibrin-network elasticity, explicit RBC-RBC and RBC-fibrin interaction energetics, osmotic effects, and platelet-generated active stress. The model is calibrated using homogeneous contraction measurements and is applied to homogeneous and heterogeneous clots in spherical, cylindrical, cubic, and flat geometries. For homogeneous clots, the model predicts that the equilibrium volume ratio is independent of clot size within the present scale-free equilibrium formulation. For heterogeneous clots, scaling the clot size while preserving the same prescribed dimensionless spatial distribution of fibrin, RBCs, and platelet activity leaves the normalized stress and strain fields, as well as the final volume ratio, unchanged. Thus, clot size alone does not determine equilibrium shrinkage in this continuum model. In contrast, when the clot size and whole-clot composition are fixed, changing the spatial distribution of RBC-rich and RBC-poor regions produces substantial changes in contraction, with the equilibrium volume ratio spanning an absolute range of approximately 0.21 in VV0 over the parameter set examined. Parameter sweeps further reveal an intermediate core-shell interface position that minimizes the equilibrium volume ratio and therefore maximizes contraction, reflecting a competition between an increasingly concentrated and mechanically resistant RBC-rich core and a deformable outer shell. These results provide a continuum mechanics framework for separating the effects of clot size, spatial heterogeneity, and whole-blood composition on clot contraction.