Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome

PLoS One. 2020 Jan 16;15(1):e0227150. doi: 10.1371/journal.pone.0227150. eCollection 2020.

Abstract

Introduction: Post-thrombotic syndrome (PTS) is a limiting long-term complication present in 20-50% of patients with deep venous thrombosis (DVT) of the lower limbs. A panel of biomarkers with potential relevance to enhance knowledge on the pathophysiology of PTS was investigated.

Methods: This case-control study included 93 patients with DVT in the lower limbs, 31 with severe PTS (cases) and 62 with mild/no PTS (controls), over 24 months after an acute episode. Thirty-one healthy individuals (HI) with no history of DVT were included as a reference to the population. FVIII activity, D-dimer, inflammatory cytokines, endothelial dysfunction markers, matrix metalloproteinases, and their inhibitors, tissue remodeling and growth factor levels were evaluated. The classification of PTS was, by the Villalta scale.

Results: Patients with severe PTS showed elevated levels of CRP, sICAM-1, sE-selectin, and decreased MMP-9 and MCP-1 levels when compared to patients with mild/no PTS. Moreover, DVT patients presented higher levels of FVIII and D-dimer when compared to HI.

Conclusions: DVT patients present an inflammatory status, endothelial dysfunction and altered proteolysis MMPs activity, even a long time after the acute thrombotic episode, which is more significant in severe PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • C-Reactive Protein / analysis*
  • Case-Control Studies
  • Chemokine CCL2 / blood*
  • E-Selectin / blood*
  • Female
  • Humans
  • Inflammation / blood
  • Intercellular Adhesion Molecule-1 / blood*
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Postthrombotic Syndrome / blood*
  • Postthrombotic Syndrome / etiology
  • Venous Thrombosis / complications

Substances

  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • E-Selectin
  • ICAM1 protein, human
  • SELE protein, human
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. JMAB also received fundings from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) - Finance Code 2016/14172-6.