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Post Deep Vein Thrombosis Vein Wall Re-Endothelialization Is Accelerated With Low Molecular Weight Heparin

Daria Moaveni, Erin Lynch, Cathy Luke, Vikram Sood, Gilbert Upchurch, Jr., Thomas Wakefield, Peter K Henke - University of Michigan, Ann Arbor, MI

Objective: Vein wall endothelial loss occurs after stasis DVT and may contribute to long term fibrotic injury. The purpose of this study was to quantify post DVT re-endothelialization and determine if low molecular weight heparin (LMWH) therapy affects this process.
Methods: Stasis DVT was generated in the rat by IVC ligation, with harvest at 1, 4, and 14 days. Immunohistological quantification of fibrotic area and luminal endothelialization was estimated by alpha SMA (aSMA) and vWF (+) staining, respectively. In separate experiments, rats were treated either pre or post-DVT with LMWH (3mg/kg daily, subQ) until harvesting at 4 days. The IVC was processed for histological analysis, or after gently removing the thrombus, processed for organ culture. In vitro stimulation of the vein wall with IL-1β (1ng/ml) was done, and the cells and supernatant processed at 48 hours for nitric oxide (NO) and prostacyclin (PC). Cells were processed by real time PCR for eNOS, iNOS, COX-1, COX-2 and thrombomodulin (TM). Comparisons were done with ANOVA or t-test.
Results: Thrombus size peaked at 4 days, and luminal re-endothelialization increased over time (2d: 11±2%, 4d: 23±4%, 14d: 64±7% (+) vWF staining; P<.01, N =5-6, compared with non DVT control). Both pre and post DVT LMWH significantly increased luminal re-endothelialization, without a difference in thrombus size (Table). Pretreatment was associated with less fibrosis (aSMA), and recovery of certain endothelial specific genes (Table). No significant difference in NO or PG levels in a supernatant was found.
Conclusions: Venous re-endothelialization occurs progressively as the DVT resolves, and can be accelerated with LMWH treatment. This may have clinical relevance for LMWH timing and treatment as compared with mechanical forms of therapy.