Incomplete resolution of deep vein thrombosis under reduced flow conditions

摘要

Introduction: Post-thrombotic syndrome is a major complication of deep vein thrombosis (DVT), occurring in up to 1/3 of first-episode DVT patients. Non-ambulatory patients have increased risk for both DVT and post-thrombotic syndrome. Experimental models are lacking that can serve as reasonable in vivo clinical analogues for poor resolution of DVT that can lead to post-thrombotic syndrome. Materials and methods: A murine model of combined DVT and reduced flow was developed that results in persistent vein wall remodeling of poorly resolved thrombus. An electrolytic-injury model of venous thrombosis was created in the femoral veins of adult CD-1 mice, either with or without upstream flow reduction (10% of normal flow), with subsequent histomorphometric and immunohistochemical evaluation out to 28 days. Results: Most venous thrombi with normal flow resolved, with little evidence of thrombus or vein wall changes 4 or more days after thrombus induction. In contrast, reduced flow had a prolonging effect on thrombus presence, resulting in long-term remodeling of the thrombus and vein wall, persistent out to 28 days. There was little evidence of monocyte or neutrophil infiltration in remodeled tissue, with only partial smooth muscle cell phenotypic presence, suggesting a fibrotic nature of the residual thrombus. Conclusions: Flow reduction inhibits thrombotic resolution in veins with resultant long-term thrombus presence and subsequent vein wall remodeling. This model may offer clinical analogy to unresolved DVT that leads to post-thrombotic syndrome.