Patient specific approach to analysis of shear-induced platelet activation in haemodialysis arteriovenous fistula

Abstract

Shear-induced platelet activation (SIPAct) is an important mechanism of thrombosis initiation under high blood flow. This mechanism relies on the interaction of platelets with the von Willebrand factor (VWF) capable of unfolding under high shear stress. High shear stress occurs in the arteriovenous fistula (AVF) commonly used for haemodialysis. A novel patient-specific approach for the modelling of SIPAct in the AVF was proposed. This enabled us to estimate the SIPAct level via computational fluid dynamics. The suggested approach was applied for the SIPAct analysis in AVF geometries reconstructed from medical images. The approach facilitates the determination of the SIPAct level dependence on both biomechanical (AVF flow rate) and biochemical factors (VWF multimer size). It was found that the dependence of the SIPAct level on the AVF flow rate can be approximated by a power law. The critical flow rate was a decreasing function of the VWF multimer size. Moreover, the critical AVF flow rate highly depended on patient-specific factors, e.g., the vessel geometry. This indicates that the approach may be adopted to elucidate patient-specific thrombosis risk factors in haemodialysis patients.

Fig 1. Overview of the SIPAct level estimation in patient-specific AVF geometries.

MRA–magnetic resonance angiography; CFD–computational fluid dynamics.

Fig 2. Patient-specific AVF geometries.

The left column (A) shows raw non-contrast enhanced MRA data. The right column (B) shows reconstructed three-dimensional AVF geometries. The white dashed rectangle in the raw MRA data delineates the zone of interest. The black arrows indicate the direction of blood flow in the AVF vessels. Blood flows into the AVF through the artery inlet (${\Gamma }_{in}^a$) and leaves the AVF through the artery (${\Gamma }_{out}^a$) and vein (${\Gamma }_{out}^v$) outlets in all CFD calculations. The P1 and P2 symbols designate the AVFs of the first and second patients, respectively.

Fig 3. Key calculated variables in the AVF P1 in systole (upper row) and diastole (lower row).

The distributions of the velocity magnitude |$\overrightarrow{V}$| (A), shear stress τ (B), cumulative shear stress CSS (C) and primed platelets P_a (D) are obtained at the highest parameter values ($Q_{out}^v$ = 725 mL/min, N = 100). The blue and red colours correspond to the lowest and highest variable values, respectively. The links for the supporting movies are available in S6 Text.

Fig 4. Key calculated variables in the AVF P2 in systole (upper row) and diastole (lower row).

The distributions of the velocity magnitude |$\overrightarrow{V}$| (A), shear stress τ (B), cumulative shear stress CSS (C) and primed platelets P_a (D) are obtained at the highest parameter values ($Q_{out}^v$ = 1300 mL/min, N = 100). The blue and red colours correspond to the lowest and highest variable values, respectively. The links for the supporting movies are available in S6 Text.

Fig 5. Dependence of the SIPAct level on the flow rate for two multimer sizes in patient-specific AVFs.

The calculation results for P1 and P2 AVFs are shown in graphs (A) and (B), respectively. The calculated points are obtained for VWF multimer sizes (N) of 10 and 100. The approximation curves (Eq (10)) are represented by the solid (N = 10) and dashed (N = 100) lines. Q_i denotes the AVF flow rate at which the approximating curves intersect. $Q_{cr}^{10}$ and $Q_{cr}^{100}$ denote the critical values of the flow rate through the fistula vein below which SIPAct was not observed for VWF multimer sizes of 10 and 100, respectively. The calculation results for intermediate values of the VWF multimer size are given in S6 Text.

Fig 6

Dependence of the SIPAct level on the VWF multimer size in P1 (A) and P2 (B) AVFs. The results are obtained at AVF flow rates ($Q_v^{out},$ Eq (7)) of 300 mL/min (dashed line) and 725 mL/min (solid line) for the first patient. The first value corresponds to the minimum flow rate required for effective haemodialysis. The second value represents the maximum AVF P1 flow rate used in the calculations. The results are obtained at AVF flow rates of 736 mL/min (dashed line) and 1300 mL/min (solid line) for the second patient. The first value corresponds to the flow rate when SIPAct is absent for the lowest VWF multimer size within the considered range (N = 10). The second value is the maximum AVF flow rate used in this work for the second patient. The solid and dashed lines are to guide the eye.

Fig 7

Parametric diagram of SIPAct in P1 (A) and P2 (B) AVFs. Region I corresponds to the values of the parameters at which no SIPAct should be observed. Region II represents the values of the parameters at which SIPAct can occur. The solid lines approximate the dependence of the critical flow rate (Q_cr) on the VWF multimer size. The value N_* (N_* = 4) is the minimum number of VWF monomers when the approach used in this work is applicable [24]. The parameter values of the approximation curves are given in S6 Text.