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Biomarkers for post thrombotic syndrome: A case-control study
Authors:AC Bouman  YW Cheung  HM Spronk  CG Schalkwijk  H ten Cate  M ten Wolde  AJ ten Cate-Hoek
Affiliation:1. Laboratory for Thrombosis and Hemostasis, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, the Netherlands;2. Department of Internal Medicine, Flevohospital, Hospitaalweg 1, Almere, the Netherlands;3. Department of Internal Medicine, Maastricht University Medical Centre, P.Debyelaan 25, Maastricht, the Netherlands
Abstract:

Introduction

There is limited knowledge on the etiology of post thrombotic syndrome (PTS), although several mechanisms have been proposed.The objectives are to explore the role of different pathogenic mechanisms for PTS, through measurement of an elaborate panel of biomarkers in patients with and without PTS.

Materials and Methods

Patients with a history of deep vein thrombosis (DVT) with PTS (cases) and without PTS after minimal 2 years follow-up (controls), were selected from the outpatient clinic of two Dutch hospitals. As a reference to the normal population healthy individuals (HI) without a history of venous thromboembolism were invited to participate. The population consisted of: 26 cases, 27 controls, and 26 HI.A panel of predefined biomarkers was measured in venous blood.

Results

D-dimer showed a decreasing trend from cases to controls to HI; p = 0.010. Thrombin/antithrombin complex levels were significantly higher in cases than in controls; p = 0.032, and HI; p = 0.017. APC-ratio was significantly lower in cases compared to controls; p = 0.032, and HI; p = 0.011. A significant trend of increasing proTAFI from cases, to controls, and HI; p = 0.002 was found. There were no differences in inflammatory markers (CRP, Interleukin-6, Interleukin-8). Thrombomodulin, tissue-plasminogen activator, and von Willebrand factor were higher in patients compared to HI. There was a significant trend of decreasing sVCAM, from cases, to controls, and HI; p = 0.029.

Conclusions

Patients with PTS displayed increased coagulation activity, an altered pattern of fibrinolytic marker expression, and increased endothelial activation. We found no evidence of systemic inflammation in patients with PTS at 63 months since the last DVT.
Keywords:A/C  anticoagulant therapy  APC  activated protein C  CRP  C-reactive protein  DVT  deep vein thrombosis  ELISA  enzyme-linked immunosorbent assay  HI  healthy individuals  Il-6/8  interleukin 6/8  IQR  interquartile range  MMP-9  matrixmetalloprotease 9  n/a  not applicable  PAI-1  tissue-plasminogen activator inhibitor type 1  PAP  plasmin-α-antiplasmin complex  proTAFI  pro thrombin activatable fibrinolysis inhibitor  PTS  post thrombotic syndrome  sICAM-1  soluble intercellular cell adhesion molecule 1  sVCAM-1  soluble vascular cell adhesion molecule 1  TAT  thrombin: antithrombin complex  TM  thrombomodulin  tPA  tissue plasminogen activator  VTE  venous thromboembolism  vWF  von Willebrand factor
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