Abstract 16021: Early Restoration of Blood Flow Improves Venous Thrombosis Resolution and Vein Wall Fibrosis: Implications for Reducing the Post-Thrombotic Syndrome

IntroductionDespite therapeutic anticoagulation, up to 50% of deep vein thrombosis (DVT) patients will develop post-thrombotic syndrome (PTS). While catheter-based endovenous therapies that induce restoration of blood flow (RBF) have the potential to reduce PTS, recent trials have demonstrated margi...

Full description

Saved in:
Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2019-11, Vol.140 (Suppl_1 Suppl 1), p.A16021-A16021
Main Authors: Li, Wenzhu, Kessinger, Chase W, Orii, Makoto, Cui, Jie, Kellnberger, Stephan, Mauskapf, Adam, Wang, Lang, Zheng, Xiaoxin, Tawakol, Ahmed A, Jaff, Michael R, Libby, Peter, Henke, Peter, Jaffer, Farouc A
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:IntroductionDespite therapeutic anticoagulation, up to 50% of deep vein thrombosis (DVT) patients will develop post-thrombotic syndrome (PTS). While catheter-based endovenous therapies that induce restoration of blood flow (RBF) have the potential to reduce PTS, recent trials have demonstrated marginal benefit. However, as aging VT are less responsive to fibrinolysis and more susceptible to vein wall fibrosis.HypothesisThe benefits of RBF on VT resolution would be time-dependent, with earlier RBF providing greater benefits.MethodsTo spur RBF, we modified a complete ligation of inferior vena cava by mechanically de-ligating the day 0 (D0) ligature at D2. Subgroups of mice received tissue plasminogen activator (tPA) 2d post de-ligation. In vivo RBF was assessed by ultrasound and venography. Measurements of VT burden, gene expression and histological assessment were done at D8. The ATTTACT trial was sub-analyzed to assess the temporal effects of pharmacomechanical catheter-directed therapy (PCDT) on PTS.ResultsDe-ligation induced RBF increased over time in mice (Fig A). The benefits of RBF on VT burden and vein wall collagen thickness (VWCT) were time-dependent, occurring only in mice exhibiting early RBF by D4 (Fig B-C). In addition, tPA reduced VT burden and VWCT only in mice without existing RBF at D4 (Fig D-E). Mice with favorable VT resolution shown reduced inflammatory and collagen mediators (Fig F-H). In the ATTRACT trial, patients receiving PCDT at earlier timepoints had lower Villalta scores and a lower incidence of moderate-to-severe PTS, but did not reach statistical significance (Fig I-J).ConclusionsEarly, but not late RBF by mechanical or pharmacological means after occlusive VT reduces murine VT burden and vein wall fibrosis. ATTRACT trial sub-analysis also suggests a potential benefit of earlier, but not later PCDT. The findings support the concept that RBF strategies designed to reduce PTS may be more effective if applied in early stage VT.
ISSN:0009-7322
1524-4539
DOI:10.1161/circ.140.suppl_1.16021