Open Access
CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2794-5116
Original Article

Biomarkers in relation to patency, popliteal reflux and post-thrombotic syndrome

Authors

  • Ruben Hupperetz

    1   Maastricht University Medical Centre+, Maastricht, Netherlands (Ringgold ID: RIN199236)
  • Aaron Iding

    2   Internal Medicine, Maastricht University Medical Centre+, Maastricht, Netherlands (Ringgold ID: RIN199236)
  • Jorinde H.H. van Laanen

    3   Vascular Surgery, Maastricht University Medical Centre+, Maastricht, Netherlands
  • Rutger Brans

    4   Radiology and Nuclear Medicine, Maastricht University Medical Centre+, Maastricht, Netherlands (Ringgold ID: RIN199236)
  • Pascale Notten

    5   Vascular Surgery, Maastricht University Medical Centre+, Maastricht, Netherlands (Ringgold ID: RIN199236)
  • Kon-Siong G Jie

    6   Internal Medicine, Zuyderland Medical Centre Sittard-Geleen, Sittard-Geleen, Netherlands (Ringgold ID: RIN159205)
  • Otmar RM Wikkeling

    7   Vascular Surgery, Hospital Nij Smellinghe, Drachten, Netherlands (Ringgold ID: RIN3011)
  • Louis-Jean Vleming

    8   Internal Medicine, Haga Hospital, Den Haag, Netherlands (Ringgold ID: RIN37134)
  • Esther Jacobs

    9   Elderly care, Proteion, Roermond, Netherlands
  • Ad Koster

    10   Internal Medicine, VieCuri Medical Centre, Venlo, Netherlands (Ringgold ID: RIN8187)
  • Cees Wittens

    11   Department of Vascular Surgery, RWTH Aachen, Aachen, Germany
    12   Department of Vascular Surgery, Maastricht University Medical Centre, Maastricht, Netherlands
  • Hugo Ten Cate

    13   Internal medicine, Maastricht University Medical Centre+, Maastricht, Netherlands (Ringgold ID: RIN199236)
  • Arina Janna Hoek-ten Cate

    14   Thrombosis expertise centre, Maastricht Universitair Medisch Centrum+, Maastricht, Netherlands (Ringgold ID: RIN199236)

Supported by: Maastricht Universitair Medisch Centrum
Supported by: ZonMw 171101001

Background 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. Objectives To investigate relationships between biomarkers, patency, popliteal reflux, and PTS. Methods This prespecified CAVA-trial subanalysis included patients with first acute iliofemoral deep vein thrombosis (DVT), randomized to standard treatment (ST) or ultrasound accelerated (UA)CDT. Baseline blood samples were analysed 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 (1y) and long-term follow-up (LT). Results Among 108 patients (51 UACDT, 57 ST), absence of patency at 1y 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. Conclusion 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.



Publication History

Received: 29 August 2025

Accepted after revision: 21 January 2026

Accepted Manuscript online:
27 January 2026

© . The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

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