Dataset Information

Postthrombotic vein wall remodeling: preliminary observations.

ABSTRACT: Postthrombotic syndrome is characterized by a fibrotic vein injury following deep vein thrombosis (DVT). We sought to quantify the change in vein wall thickness in patients who fail to resolve DVT by 6 months and whether there were differences in blood or plasma levels of inflammatory proteins associated with venous remodeling.Patients presenting with confirmed lower extremity DVT were prospectively recruited for this study. Duplex imaging of the lower extremity venous system was performed, and blood was collected at entrance and repeat evaluation with blood draw and ultrasound imaging at 1 and 6 months. DVT resolution and thickness of the vein wall was quantified by ultrasound imaging in each segment affected by thrombus, and a contralateral, unaffected vein wall served as a control. Gene and protein expression of inflammatory markers were examined from leukocytes and serum, respectively. Analysis of variance or Student t-tests were used, and a P < .05 was significant. N = 10 to 12 for all analyses.Thirty-two patients (12 patients with DVT resolution at 6 months, 10 patients with persistent thrombus at 6 months, and 10 healthy controls) were compared. Both resolving and nonresolving DVT were associated with a 1.5- to 1.8-fold increased vein wall thickness at 6 months (P = .008) as compared with nonaffected vein wall segments. However, the thickness of the affected segments was 1.4-fold greater in patients who had total resolution of the DVT by 6 months than in patients who had persistent chronic thrombus 6 months after presentation (P = .01). There was a four- to five-fold increased level of matrix metalloproteinase-9 (MMP-9) antigen in thrombosed patients compared with nonthrombosed patient controls (P < .05), while Toll-like receptor-9 (TLR-9) gene expression was three-fold less than controls (P < .05) at enrollment. D-dimer and P-selectin were higher in thrombosed as compared to controls at diagnosis but not at 6 months. Both TLR-4 (marker of inflammation) and P-selectin gene expression were higher in leukocytes from patients with chronic DVT compared with those who resolved at 1 month after diagnosis (P < .05).This preliminary study suggests ongoing vein wall remodeling after DVT, measurable by ultrasound and associated with certain biomarkers. At 6 months, the vein wall is markedly thickened and directly correlates with resolution. This suggests that the vein wall response is initiated early following thrombus formation and persists even in the presence of total resolution.

SUBMITTER: Deatrick KB

PROVIDER: S-EPMC3010467 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Postthrombotic vein wall remodeling: preliminary observations.

Deatrick Kristopher B KB Elfline Megan M Baker Nichole N Luke Catherine E CE Blackburn Susan S Stabler Catherine C Wakefield Thomas W TW Henke Peter K PK

Journal of vascular surgery 20100924 1

<h4>Background</h4>Postthrombotic syndrome is characterized by a fibrotic vein injury following deep vein thrombosis (DVT). We sought to quantify the change in vein wall thickness in patients who fail to resolve DVT by 6 months and whether there were differences in blood or plasma levels of inflammatory proteins associated with venous remodeling.<h4>Methods</h4>Patients presenting with confirmed lower extremity DVT were prospectively recruited for this study. Duplex imaging of the lower extremit ...[more]

PMID: 20869834

Similar Datasets

Project description:BackgroundVein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP2 contributes to vein wall remodeling after VT is unknown.MethodsStasis VT was produced by ligation of the inferior vena cava and tissue was harvested at 2, 8, and 21 days in MMP2 -/- and genetic wild type (WT) mice. Tissue analysis by immunohistochemistry, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and zymography was performed.ResultsThrombus resolution was less at 8 days in MMP2 -/- compared with WT, evidenced by a 51% increase in VT size (P < .01), and threefold fewer von Willebrand's factor positive channels (P < .05). In MMP2 -/- mice, the main phenotypic fibrotic differences occurred at 8 days post-VT, with significantly less vein wall collagen content (P = .013), fourfold lower procollagen III gene expression (P < .01), but no difference in procollagen I compared with WT. Decreased inflammation in MMP2 -/- vein walls was suggested by ∼ threefold reduced TNFα and IL-1β at 2 days and 8 days post-VT (P < .05). A fourfold increase in vein wall monocytes (P = .03) with threefold decreased apoptosis (P < .05), but no difference in cellular proliferation at 8 days was found in MMP2 -/- compared with WT. As increased compensatory MMP9 activity was observed in the MMP2 -/-mice, MMP2/9 double null mice had thrombus induced with VT harvest at 8 days. Consistently, twofold larger VT, a threefold decrease in vein wall collagen, and a threefold increase in monocytes were found (all P < .05). Similar findings were observed in MMP9 -/- mice administered an exogenous MMP2 inhibitor.ConclusionsIn stasis VT, deletion of MMP2 was associated with less midterm vein wall fibrosis and inflammation, despite an increase in monocytes. Consideration that VT resolution was impaired with MMP2 (and MMP2/9) deletion suggests direct inhibition will likely also require anticoagulant therapy.

Project description:BackgroundChronic kidney disease (CKD) is a highly comorbid condition with significant effects on vascular health and remodeling. Upper extremity veins are important in end-stage kidney disease (ESKD) due to their potential use to create vascular accesses. However, unlike arteries, the contribution of CKD-associated factors to the chronic remodeling of veins has been barely studied.MethodsWe measured morphometric parameters in 315 upper extremity veins, 131 (85% basilic) from stage 5 CKD/ESKD patients and 184 (89% basilic) from non-CKD organ donors. Associations of demographic and clinical characteristics with intimal hyperplasia (IH) and medial fibrosis were evaluated using multivariate regression models.ResultsThe study cohort included 33% females, 30% blacks, 32% Hispanics, and 37% whites. Over 60% had hypertension, and 25% had diabetes independent of CKD status. Among kidney disease participants, 26% had stage 5 CKD, while 22 and 52% had ESKD with and without history of a previous arteriovenous fistula/graft (AVF/AVG), respectively. Intimal hyperplasia was associated with older age (β = 0.13 per year, confidence interval [CI] = 0.002-0.26), dialysis vintage > 12 months (β = 0.22, CI = 0.09-0.35), and previous AVF/AVG creation (β = 0.19, CI = 0.06-0.32). Upper quartile values of IH were significantly associated with diabetes (odds ratio [OR] = 2.02, CI = 1.08-3.80), which demonstrated an additive effect with previous AVF/AVG history and longer vintage in exacerbating IH. Medial fibrosis also increased as a function of age (β = 0.17, CI = 0.04-0.30) and among patients with diabetes (β = 0.15, CI = 0.03-0.28). Age was the predominant factor predicting upper quartile values of fibrosis (OR = 1.03 per year, CI = 1.01-1.05) independent of other comorbidities.ConclusionAge and diabetes are the most important risk factors for chronic development of venous IH and fibrosis independent of CKD status. Among kidney disease patients, longer dialysis vintage, and history of a previous AVF/AVG are strong predictors of IH.

Dataset Information

Postthrombotic vein wall remodeling: preliminary observations.

Publications

Postthrombotic vein wall remodeling: preliminary observations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets