Objective
Venous thromboembolism frequently results in thrombi formation near or within the pocket of a venous valve as the result of recirculating hemodynamics, which has been largely attributed to hypoxia-induced tissue factor (TF) expression. Numerical models are now capable of assessing the spatiotemporal behavior of the TF initiated coagulation cascade under non-uniform hemodynamics. The aim of this study was to use such a numerical simulation to analyze the degree and location of thrombin formation with respect to tissue factor position in the presence of disturbed flow induced by an open venous valve.
Method
Thrombin formation was simulated using a computational model that captures the hemodynamics, kinetics and chemical transport of 22 biochemical species. Disturbed flow is described by the presence of a valve in the equilibrium phase of the valve cycle with leaflets in a fully open position. Three different positions of TF downstream of the valve opening were investigated.
Results
The critical amount of TF required to initiate a thrombotic response is reduced by up to 80% when positioned underneath the recirculating regions near the valve opening. Additionally, due to the increased surface area of the open valve cusp, in conjunction with recirculating hemodynamics, it was observed that thrombin is generated inside the valve pocket even when the exposed region of TF is downstream of the valve.
Conclusions
The presence of pro-thrombotic surface reactions, in conjunction with recirculating hemodynamics, provides an additional mechanism for thrombus formation in venous valves, which does not require direct damage or dysfunction to the valve itself.