Simulated thrombin responses in venous valves

Abstract

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.

Numerical simulation of blood fluid in hemodialysis catheters and its thrombogenic potential

“…In the presence of thrombosis, the internal resistance to the flow increases and it may lead to a flow of less than 300 mL min. -1 , which is the recommended mean flow to circulate inside the CVC when hemodialysis occurs (Browne et al, 2015;Dydek & Chaikof, 2016). In addition, it may occur a more negative flow pressure than -250 mmHg in the arterial orifices, which is a rate considered as ideal in sites where the patient's filtered blood returns to the hemodialysis machine (Sarmast et al, 2014).…”

“…Care should be taken when the negative pressure of the fluid increases, as it increases the resistance to blood filtration when on hemodialysis. In clinical practice, mechanical attempts to manipulate the catheter in order to improve such resistance to blood flow due to CVC dysfunction may cause a disturbance of the fibrinolytic system and promote inflammatory processes and activation of the coagulation cascade (Sarmast et al, 2014;Dydek & Chaikof, 2016).…”

“…A study in China that performed a numerical simulation of CVC inserted into the vein found that maintaining the catheter within the vein led to a significant increase in pressure and an abnormally high shear stress in the vessel wall (Peng et al, 2017). The term 'abnormally high' refers to the physiological comparison of shear stress within the vein without the CVC ranging from 0.1 to 1 Pa (Peng et al, 2017;Lee et al, 2016, Dydek, & Chaikof, 2016. However, that study did not construct the actual CVC geometry with the lateral orifices and the central division within the catheter.…”

“…The dynamics of computational fluids allows the investigation of hemodynamic factors such as velocity, pressure and shear stress which can lead to an acceleration, modulation and progression of thrombus formation (Lucas et al, 2014;Browne et al, 2015). Numerical simulation studies evaluated the performance and necessity of lateral orifices in angiographic, thrombus-aspiration catheters and venous cannulas (Lucas et al, 2014;Dydek & Chaikof, 2016).…”

“…A computer simulation study evaluated the formation of thrombi in venous valves due to the presence of blood circulation areas that can stimulate the expression of the Tissue Factor (TF) and consequent initiation of the coagulation process (Dydek & Chaikof, 2016). It was found that, in recirculation areas, thrombin was generated and a thrombotic response was initiated (Dydek & Chaikof, 2016).…”