Biomarkers for post thrombotic syndrome: A case-control study

• Published in: Thrombosis research Vol. 134; no. 2; pp. 369 - 375
• Main Authors: Bouman, A.C, Cheung, Y.W, Spronk, H.M, Schalkwijk, C.G, ten Cate, H, ten Wolde, M, ten Cate-Hoek, A.J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.08.2014
• Subjects: Aged; Biomarkers; Biomarkers - blood; Blood Coagulation; Case-Control Studies; Case-control study; Etiology; Female; Fibrin Fibrinogen Degradation Products - analysis; Hematology, Oncology and Palliative Medicine; Humans; Male; Middle Aged; Post thrombotic syndrome; Postthrombotic Syndrome - blood; Postthrombotic Syndrome - complications; Postthrombotic Syndrome - diagnosis; Thrombin - analysis; Venous thrombosis; Venous Thrombosis - blood; Venous Thrombosis - complications; CRP; HI; n/a; C-reactive protein; DVT; tissue plasminogen activator; vWF; TAT; VTE; pro thrombin activatable fibrinolysis inhibitor; Case-control study; interquartile range; matrixmetalloprotease 9; sVCAM-1; Il-6/8; interleukin 6/8; PTS; soluble intercellular cell adhesion molecule 1; sICAM-1; Etiology; von Willebrand factor; proTAFI; PAI-1; plasmin-α-antiplasmin complex; thrombin: antithrombin complex; Venous thrombosis; post thrombotic syndrome; anticoagulant therapy; not applicable; tPA; IQR; tissue-plasminogen activator inhibitor type 1; soluble vascular cell adhesion molecule 1; deep vein thrombosis; APC; A/C; venous thromboembolism; enzyme-linked immunosorbent assay; thrombomodulin; Biomarkers; TM; healthy individuals; MMP-9; PAP; activated protein C; ELISA; Post thrombotic syndrome
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2014.06.010

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.