Abstract 354: Early Intentional Restoration of Blood Flow Reduces Thrombus Burden and Vein Wall Scarring Following Dvt: Implications for Preventing the Post-thrombotic Syndrome

Abstract

Background: Despite anticoagulation therapy, up to 50% of deep vein thrombosis (DVT) patients still develop the post-thrombotic syndrome (PTS), a condition that arises from thrombus obstruction and vein wall damage, leading to venous hypertension. While catheter-based intervention may reduce PTS, the CaVenT and ATTRACT trials demonstrated little clinical benefit of intentional restoration of blood flow (RBF) for reducing PTS. However, these trials have not explored the time-dependence of RBF, a key factor as aging VT are associated with greater vein wall injury. Methods: To investigate the temporal effects of intentional RBF following VT, we modified a classic complete ligation inferior vena cava (IVC) stasis VT protocol in C57BL/6 mice by de-ligating the day 0 ligature at day 2 to allow RBF. Compared to intravital microscopy, the sensitivity and specificity of noninvasive ultrasound (US) to detect RBF was 82.1% and 94.4%, respectively. Serial US was then performed on mice. Mice were classified as early RBF (RBF by day 4), late RBF (RBF after day 4), no RBF, or sham de-ligation groups. Follow day 8 sacrifice, thrombus burden (mg/cm) and vein wall scarring (VWS) were measured. Kruskal-Wallis followed by Dunn’s test was used to compare statistical significance between groups. Results: After de-ligation, RBF through VT increased gradually over time (Fig. A). The early RBF group exhibited significant reductions in VT burden (N=9) and VWS (N=5) at day 8 ( p <0.05 vs. comparator groups, Fig B-C). In contrast, the late RBF group did not experience significant reductions in thrombus burden (N=6) nor VWS (N=4), with measures similar to mice with no RBF (N=3-4), or sham de-ligation (N=8-9). Conclusions: Intentional early RBF reduces venous thrombus burden and VWS, factors that drive PTS. Mechanistic studies to address these findings are going. The overall results suggest that anti-PTS benefits of catheter-based intervention may be enhanced in subjects receiving early RBF.