Abstract 19793: Pulsatility Modulates the Acquired Von Willebrand Factor Defect Related to Mechanical Circulatory Support Devices

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Abstract

Introduction: Bleeding is the most frequent adverse event observed in patients with continuous-flow mechanical circulatory support (CF-MCS). The main risk factor of bleeding is the acquired Von Willebrand factor (VWF) defect related to the high shear stress forces developed by these devices. Although a higher bleeding rate has been reported by different groups in CF-MCS supported patients who had reduced arterial pulsatility (AP), the relation between AP and the intensity of acquired VWF defect has never been studied. Our objective was to investigate the relation between AP and VWF.

Hypothesis: The AP modulates the VWF multimeric profile under CF-MCS.

Methods:In vitro, in an endothelial-free mock circulatory loop, we assessed the impact of two high shear CF-MCS (MCS-A and MCS-B adapted respectively from Impella-CP and Impella-5.0) on VWF multimers degradation. Using these devices, we investigated in a swine model, the impact of various AP on VWF. The different AP levels were obtained by the combination of the maximum flow of the device and its localization either in the left ventricle (reduction of AP) or in the aorta (AP preserved). In a dose-effect model, we investigated three different levels of AP. In a cross-over model, we studied in each animal the effects of sequential changes of AP on VWF parameters.

Results:In vivo, in the cross over model, we observed in constant high shear stress level condition that the magnitude of the VWF loss is modulated by the AP level and that the restoration of AP is a trigger for an endothelial release of VWF (fig 1).

Conclusions: We demonstrated that AP is a trigger of endothelial release of VWF. The VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release triggered by the AP. This direct modulation of VWF defect could explain the relationship between AP and bleeding in patients receiving CF-MCS.

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