March 3, 2026Open Access

Biomarkers in Relation to Patency, Popliteal Reflux, and Post-thrombotic Syndrome: A Subanalysis of the Ultrasound-accelerated Catheter-directed Thrombolysis versus Anticoagulation for the Prevention of Post-thrombotic Syndrome Trial

Key Points

Absence of patency at 1-year correlates with higher baseline CRP and fibrinogen levels.
Elevated IL-6 and VEGF-A levels were linked to reduced patency in standard treatment patients.

Structured PICO

Does ultrasound accelerated catheter-directed thrombolysis alter the relationship between baseline biomarkers and patency, popliteal reflux, or post-thrombotic syndrome compared to standard treatment in patients with acute iliofemoral DVT?

Population

108 patients with first acute iliofemoral deep vein thrombosis (DVT)

Intervention

Ultrasound accelerated catheter-directed thrombolysis (UACDT)

Comparator

Standard treatment (ST) (anticoagulation)

Outcome

Patency and popliteal reflux (assessed by duplex ultrasound), and post-thrombotic syndrome (assessed by Villalta score) at 1-year and long-term follow-up in relation to baseline biomarkerssurrogate

Baseline inflammatory and tissue remodeling biomarkers are associated with patency, reflux, and post-thrombotic syndrome outcomes, suggesting biomarker profiles could eventually guide patient selection for catheter-directed thrombolysis.

Abstract

Despite restored patency, catheter-directed thrombolysis (CDT) has variable efficacy in preventing post-thrombotic syndrome (PTS); biomarkers may clarify PTS pathophysiology and guide patient selection for CDT.To investigate relationships between biomarkers, patency, popliteal reflux, and PTS.This prespecified CAVA trial subanalysis included patients with first acute iliofemoral deep vein thrombosis (DVT), randomized to standard treatment (ST) or ultrasound accelerated CDT (UACDT). Baseline blood samples were analyzed for fibrinogen, CRP, IL-6, IL-10, VEGF-A, P-selectin, E-selectin, ICAM-1, VCAM-1, MMP-2, MMP-9, and adiponectin. Patency and reflux (duplex ultrasound), and PTS (Villalta score) were assessed at 1-year and long-term follow-up (LT).Among 108 patients (51 UACDT, 57 ST), absence of patency at 1-year was associated with higher baseline CRP and fibrinogen in both groups, and elevated IL-6 and VEGF-A in the ST group. Reflux at LT was associated with lower IL-6 and adiponectin in the UACDT group. (Moderate-to-severe) PTS at LT was associated with higher baseline MMP-2 and lower IL-10 in the UACDT group, and lower baseline VCAM-1 and adiponectin in the ST group.Pro-inflammatory processes are linked to reduced patency, with UACDT improving patency in patients with enhanced inflammatory responses. LT reflux is associated with impaired vasoprotective properties. PTS involves impaired anti-inflammatory responses and tissue remodelling both not modifiable by UACDT. Therefore, biomarker-guided treatment selection may potentially improve treatment outcome.

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