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Biomarkers for post thrombotic syndrome: A case-control study
Authors:A.C. Bouman  Y.W. Cheung  H.M. Spronk  C.G. Schalkwijk  H. ten Cate  M. ten Wolde  A.J. 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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