Characterization of Arteriovenous Thrombus Formation and Propagation in a Mouse Arteriovenous Fistula Model

Compared with an arterial thrombus (AT) or a venous thrombus (VT), there is limited knowledge about arteriovenous thrombus (AVT). AVT develops in 69% of arteriovenous fistulae (AVF) and 50% of arteriovenous grafts (AVG) within 1 year. Thrombosis remains one of the major complications after creation of a vascular access often resulting in failure of the access.To characterize and differentiate AVT from VT or AT.An AVT model was established by a needle puncture through the aorta to the inferior vena cava (IVC) in wild type mice and different reporter mice and compared with a mouse venous thrombus (VT) model using IVC ligation. AVT was also examined under defined arteriovenous flow conditions. AVT was examined by gross view, histology, immunofluorescence, and scanning electron microscopy.AVT occurs immediately at the juxta-anastomotic area (JAA) after successful arteriovenous flow was established, with platelets being a major component of early AVT. Reduced injury to the endothelium resulted in smaller AVT, whereas local delivery of rapamycin to inhibit cell proliferation failed to decrease the volume of the AVT. Incomplete reendothelialization of the peri-fistula exit area correlated with growth of the AVT. AVT universally presents at the JAA in other arteriovenous models.We provide the first detailed histopathological characterization of AVT induced by AVF. AVT originates from the injured vessel wall and is more similar to AT than VT. This model provides a valuable tool to characterize AVT. Both this AVT model and our data have potential for clinical translation.