Development and validation of a mathematical model for evaluating shear-induced damage of von Willebrand factor

To develop a mathematical model for predicting shear-induced von Willebrand factor (vWF) function modification which can be used to guide ventricular assist devices (VADs) design, and evaluate the damage of high molecular weight multimers (HMWM)-vWF in VAD patients for reducing clinical complications.

Mathematical models were constructed based on three morphological variations (globular vWF, unfolded vWF and degraded vWF) of vWF under shear stress conditions, in which parameters were obtained from previous studies or fitted by experimental data. Different clinical support modes (pediatric vs. adult mode), different VAD operating states (pulsation vs. constant mode) and different clinical VADs (HeartMate II, HeartWare and CentriMag) were utilized to analyze shear-induced damage of HMWM-vWF based on our vWF model. The accuracy and feasibility of the models were evaluated using various experimental and clinical cases, and the biomechanical mechanisms of HMWM-vWF degradation induced by VADs were further explained.

The mathematical model developed in this study predicted VAD-induced HMWM-vWF degradation with high accuracy (correlation with experimental data r² > 0.99). The numerical results showed that VAD in the pediatric mode resulted in more HMWM-vWF degradation per unit time and per unit flow rate than in the adult mode. However, the total degradation of HMWM-vWF is less in the pediatric mode than in the adult mode because the pediatric mode has fewer times of blood circulation than the adult mode in the same amount of time. The ratio of HMWM-vWF degradation was lower in the pulsation mode than in the constant mode. This is due to the increased flushing of VADs in the pulsation mode, which avoids prolonged stagnation of blood in high shear regions. This study also found that the design feature, rotor size and volume of the VADs, and the superimposed regions of high shear stress and long residence time inside VADs affect the degradation of HMWM-vWF. The axial flow VADs (HeartMate II) showed higher degradation of HMWM-vWF compared to centrifugal VADs (HeartWare and CentriMag). Compared to fully magnetically suspended VADs (CentriMag), hydrodynamic suspended VADs (HeartWare) produced extremely high degradation of HWMW-vWF in its narrow hydrodynamic clearance. Finally, the study used a mathematical model of HMWM-vWF degradation to interpret the clinical statistics from a biomechanical perspective and found that minimizing the rotating speed of VADs within reasonable limits helps to reduce HWMW-vWF degradation. All predicted conclusions are supported by the experimental and clinical data.

This study provides a validated mathematical model to assess the shear-induced degradation of HMWM-vWF, which can help to evaluate the damage of HMWM-vWF in patients implanted with VADs for reducing clinical complications, and to guide the optimization of VADs for improving hemocompatibility.