Impact of altered venous hemodynamic conditions on the formation of platelet layers in thromboemboli

Although it is generally believed that the structure of venous thromboemboli is a homogeneous red blood cell-fibrin clot, their structure may be heterogeneous, with non-uniformly distributed platelet layers, known as the lines of Zahn. We tested (a) whether venous thromboemboli ex vivo contained platelet layers, i.e. the lines of Zahn, and (b) whether, according to mathematical modeling, eddies can arise in the venous system, possibly contributing to platelet aggregation. The structure of venous thromboemboli ex vivo was determined by high-resolution magnetic resonance imaging (MRI) and by immunohistochemistry (IHC). High-resolution ultrasound (US) imaging was employed to determine the popliteal vein geometry and hemodynamics in healthy subjects and in subjects with previous venous thrombosis. The US data were then used as input for numerical simulations of venous hemodynamics. MRI and IHC confirmed that 42 of 49 ex vivo venous thromboemboli were structurally heterogeneous with platelet layers. The peak venous flow velocity was higher in patients with partly recanalized deep vein thrombosis than in healthy subjects in the prone position (46 ± 4 cm/s vs. 16 ± 3 cm/s). Our numerical simulation showed that partial venous obstruction with stenosis or malfunctioning venous valves creates the conditions for eddy blood flow. Our experimental results and computer simulation confirmed that the heterogeneous structure of venous thromboemboli with twisted platelet layers may be associated with eddy flow at the sites of their formation.