Abstract 10282: Early Anticoagulation Improves Post-Thrombotic Syndrome Outcomes and Experimental Restoration of Blood Flow in DVT Subjects

Introduction: Despite anticoagulation (AC), up to 50% of proximal deep vein thrombosis (DVT) patients will develop the post-thrombotic syndrome (PTS). In a substudy of the ATTRACT DVT trial, catheter-directedthrombectomy/thrombolysis (CDT) in addition to AC improved PTS outcomes for patients presenting at an intermediate day (D) 4-8 symptom-onset-to-randomization (SOR) timeframe, but not at an early D0-3 or late D9+ SOR timeframe. Mechanisms underlying the role of early AC and CDT are unknown, particularly iliofemoral DVT (IFDVT) patients that preferentially benefit from CDT. Methods: First, we assessed the temporal impact of AC on Villalta and VEINES-QoL PTS scores in a post-hoc analysis of the IFDVT ATTRACT patients (N=391). Mean scores were estimated by a piecewise linear-regression growth-curve model. Next, to mechanistically explore the effects of AC on PTS measures, C57/BL6 mice (N=76) underwent inferior vena cava (IVC) ligation to produce stasis DVT. Mice then underwent true or sham de-ligation at D2 to spur restoration of blood flow (RBF). Last, enoxaparin AC was initiated at D2 and given daily until D8, at either 0, 10, or 30 mg/kg/d SQ. D4 RBF rates in the IVC, and D8 thrombus burden were assessed. Results: In IFDVT ATTRACT patients, CDT+AC improved PTS scores in the intermediate D4-8 SOR timeframe (p<0.001 vs. AC alone). However, in the early D0-3 SOR timeframe, CDT+AC did not improve PTS scores (p>0.05 vs. AC alone). In the AC alone groups, early AC D0-3 significantly improved PTS scores over delayed AC (p<0.05). In sham de-ligated mice with IVC DVT, D2 enoxaparin improved D4 RBF rates (sham, 11.1%; low-dose, 33.3%; high-dose, 40.0%). D2 enoxaparin also significantly reduced D8 thrombus weight (p<0.05, both doses vs. saline). However, in true de-ligation mice, D2 enoxaparin only mildly increased D4 RBF rates (sham, 50%; low-dose, 61.5%; high-dose, 60%), and did not decrease D8 thrombus weight (p>0.05). Conclusions: In ATTRACT patients presenting with IFDVT at an early D0-3 SOR timeframe, PTS outcomes were improved by AC but not further improved by CDT. Experimentally, early D2 AC initiation can improve RBF rates and DVT resolution. These findings suggest that achieving early RBF may reduce the risk of PTS.