Endothelium-biomarkers for postthrombotic syndrome: a case-control study.

ABSTRACT

BACKGROUND: The postthrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT). Increase knowledge on the PTS pathophysiology and novel biomarkers are needed in order to predict PTS development and to improve treatment results. The aim of this study was to analyze novel endothelium-biomarkers for PTS in patients with DVT out of the acute phase. METHODS: A case-control study was conducted. Inclusion criteria were symptomatic and confirmed DVT patients treated with anticoagulants for at least 3 months. Villalta score was performed at the time of inclusion and used to diagnose and classify the severity of PTS. Plasma inter-cellular adhesion molecule 1 (ICAM-1), P-selectin, fractalkine and vascular endothelial growth factor (VEGF) were quantified using cytometric bead array. Endothelial progenitor cells (EPCs) and circulating endothelial cells (CEC) level were quantified by flow cytometry. RESULTS: Thirty two patients and 61 controls were included. PTS patients showed higher levels of CEC (0.56/µl (0.34-1.5) vs. 0.20/µl (0.11-0.77); P  = 0.04) and EPC (0.75/µl (0.38-1.52) vs. 0.09/µl (0.05-0.82); P  = 0.0021) compared to no PTS patients. Patients with PTS had significantly higher levels of fractalkine (387.60 pg/ml (222.30-597.90) vs. 98.00 pg/ml (82.30-193.02); P  = 0.044) than patients without PTS. Fracktalkine levels showed a strong linear correlation with Villalta score, r  = 0.86, P  < 0.0001. No differences were observed in P-selectin, ICAM-1 and VEGF between studied groups. CONCLUSIONS: The formation and early resolution of DVT are characterized by inflammation and endothelial/platelet activation. We have identified possible novel biomarkers such as CEC, EPC and fractalkine for the development of PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS turning them into potential therapeutic targets.