Symmetry-breaking flow transition as an under-recognized hemodynamic factor in valve-associated thrombosis

Venous thrombosis commonly develops near venous valve pockets, where disturbed hemodynamics and reduced washout create spatially heterogeneous flow environments. Conventional descriptions of this region emphasize continuously varying quantities such as velocity, shear stress, recirculation, and residence time, but do not address whether post-valve flow can transition between distinct organized states. Here, we combine computational and experimental vein-on-a-chip approaches to resolve Reynolds-number-dependent post-valve flow organization and its downstream transport consequences. In a geometrically symmetric rigid valve, increasing Reynolds number triggered a symmetrybreaking transition from a centered jet to a persistent asymmetric flow state, with repeatable separation between the increasing- and decreasing-Reynolds-number branches under transient forcing. Valve compliance delayed this transition by increasing the effective opening and reducing local inertial forcing, whereas a small bilateral geometric bias promoted earlier branch selection. Fluid-structure interaction further showed that, after symmetry breaking, unequal hydrodynamic loading generated unequal leaflet deformation, providing a mechanism for structural reinforcement of the selected flow state. The Reynolds-number-dependent ordering was reproduced experimentally and remained detectable in whole blood. Downstream transport of RBC-scale particles exhibited a delayed but persistent lateral redistribution relative to the velocity-field response. These results identify post-valve symmetry breaking as a flow-state transition regulated by local inertial forcing, valve mechanics, and geometric bias. Venous-valve hemodynamics can therefore transition between distinct flow states, providing a physical basis for how small mechanical or geometric differences can generate persistent transport heterogeneity relevant to thrombosis.