Download PDF
Open Access
CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2794-5116
Original Article: Stroke, Systemic or Venous Thromboembolism

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

Authors

  • Ruben D. Hupperetz 

    1   Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center (MUMC + ), Maastricht, The Netherlands
    2   Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands

  • Aaron F. J. Iding

    1   Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center (MUMC + ), Maastricht, The Netherlands
    2   Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
    3   Department of Internal Medicine, MUMC + , Maastricht, The Netherlands

  • Jorinde van Laanen

    4   Department of Vascular Surgery, MUMC + , Maastricht, The Netherlands

  • Rutger Brans

    5   Department of Radiology, MUMC + , Maastricht, The Netherlands

  • Pascale Notten 

    2   Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
    4   Department of Vascular Surgery, MUMC + , Maastricht, The Netherlands

  • Jie Asiong

    6   Department of Internal Medicine, Zuyderland Medical Center, Sittard, The Netherlands

  • Otmar R. M. Wikkeling

    7   Department of Vascular Surgery, Nij Smellinghe Hospital, Drachten, The Netherlands
    8   Department of Surgery, Frisius Medical Center, Leeuwarden, The Netherlands

  • Louis-Jean Vleming

    9   Department of Internal Medicine, Haga Hospital, the Hague, The Netherlands

  • Esther M. G. Jacobs

    10   Elderly Care, Proteion, Roermond, The Netherlands

  • Ad Koster

    11   Department of Internal Medicine, VieCuri Medical Center, Venlo, The Netherlands

  • Cees Wittens

    12   Phlebological Center Grave, Grave, The Netherlands

  • Hugo ten Cate

    1   Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center (MUMC + ), Maastricht, The Netherlands
    2   Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
    3   Department of Internal Medicine, MUMC + , Maastricht, The Netherlands
    13   Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

  • Arina J. ten Cate-Hoek

    1   Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center (MUMC + ), Maastricht, The Netherlands
    2   Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands
Further Information
  Permissions and Reprints


Graphical Abstract

Abstract

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 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).

Results

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.

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.

Keywords

peripheral catherization - post-thrombotic syndrome - biomarkers/blood - vascular patency - venous thrombosis

Contributors' Statement

R.H., A.I., and A.T.C. performed the data analysis and interpretation; R.H. and A.T.C. wrote the manuscript; A.T.C., H.T.C., and C.H.A.W. contributed to study concept and study design of the CAVA trial. All other authors contributed equally to data collection and review of the manuscript. Authors involved in analyzing the data (R.H., A.I., and A.T.C.) had full access to all of the study data. A.T.C. had final responsibility for the decision to submit for publication. All authors approved the final version for submission.


Supplementary Material



Publication History

Received: 29 August 2025

Accepted: 21 January 2026

Accepted Manuscript online:
27 January 2026

Article published online:
10 February 2026

© 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/)

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany