Fibrinolysis; PAI-1; Sensitivity and specificity; TAFI; Venous Thromboembolism
Abstract :
[en] BACKGROUND: Both activated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and active Plasminogen Activator Inhibitor-1 (PAI-1) attenuate fibrinolysis and may therefore contribute to the pathophysiology of Venous ThromboEmbolism (VTE). Whether increased TAFI and/or PAI-1 concentrations are associated with VTE is unclear. OBJECTIVE: To study an association of impaired fibrinolysis and VTE using a comprehensive panel of in-house developed assays measuring intact TAFI, activation peptide of TAFI (AP-TAFI), PAI-1 antigen, endogenous PAI-1:t-PA complex (PAI-1:t-PA) and active PAI-1 levels in 102 VTE patients and in 113 healthy controls (HC). RESULTS: Active PAI-1 was significantly higher in VTE patients compared to HC (20.9 [9.6-37.8] ng/ml vs. 6.2 [3.5-9.7] ng/ml, respectively). Active PAI-1 was the best discriminator with an area under the ROC curve and 95% confidence interval (AUROC [95%CI]) of 0.84 [0.79-0.90] compared to 0.75 [0.68-0.72] for PAI-1:t-PA, 0.65 [0.58-0.73] for PAI-1 antigen, 0.62 [0.54-0.69] for AP-TAFI and 0.51 [0.44-0.59] for intact TAFI. Using ROC analysis, we defined an optimal cut-off of 12.8 ng/ml for active PAI-1, with corresponding sensitivity of 71 [61-79] % and specificity of 89 [82-94] %. A lack of association with the time between VTE event and sample collection or with the intake of anticoagulant treatment suggests that active PAI-1 levels are sustainable high in VTE patients. CONCLUSIONS: This case-control study emphasizes the clinical importance of measuring active PAI-1 instead of PAI-1 antigen and identifies active PAI-1 as a potential marker of VTE. Prognostic studies will need to address the clinical significance of active PAI-1 as biomarker.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Bollen, Lize
Peetermans, Marijke
Peeters, Miet
Van Steen, Kristel ; Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Hoylaerts, Marc F.
Declerck, Paul J.
Verhamme, Peter
Gils, Ann
Language :
English
Title :
Active PAI-1 as marker for venous thromboembolism: case-control study using a comprehensive panel of PAI-1 and TAFI assays.
Publication date :
2014
Journal title :
Thrombosis Research
ISSN :
0049-3848
eISSN :
1879-2472
Publisher :
Elsevier, United Kingdom
Volume :
134
Issue :
5
Pages :
1097-102
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2014 Elsevier Ltd. All rights reserved.
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