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Active PAI-1 as marker for venous thromboembolism: case-control study using a comprehensive panel of PAI-1 and TAFI assays.
Thromb Res. 2014 Nov; 134(5):1097-102.TR

Abstract

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.

Authors+Show Affiliations

Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium.Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, UZ Leuven, Belgium.Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium.Systems and Modeling Unit, Montefiore Institute, University of Liège, Belgium.Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, UZ Leuven, Belgium.Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium.Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, UZ Leuven, Belgium.Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium. Electronic address: ann.gils@pharm.kuleuven.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25193405

Citation

Bollen, Lize, et al. "Active PAI-1 as Marker for Venous Thromboembolism: Case-control Study Using a Comprehensive Panel of PAI-1 and TAFI Assays." Thrombosis Research, vol. 134, no. 5, 2014, pp. 1097-102.
Bollen L, Peetermans M, Peeters M, et al. Active PAI-1 as marker for venous thromboembolism: case-control study using a comprehensive panel of PAI-1 and TAFI assays. Thromb Res. 2014;134(5):1097-102.
Bollen, L., Peetermans, M., Peeters, M., Van Steen, K., Hoylaerts, M. F., Declerck, P. J., Verhamme, P., & Gils, A. (2014). Active PAI-1 as marker for venous thromboembolism: case-control study using a comprehensive panel of PAI-1 and TAFI assays. Thrombosis Research, 134(5), 1097-102. https://doi.org/10.1016/j.thromres.2014.08.007
Bollen L, et al. Active PAI-1 as Marker for Venous Thromboembolism: Case-control Study Using a Comprehensive Panel of PAI-1 and TAFI Assays. Thromb Res. 2014;134(5):1097-102. PubMed PMID: 25193405.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Active PAI-1 as marker for venous thromboembolism: case-control study using a comprehensive panel of PAI-1 and TAFI assays. AU - Bollen,Lize, AU - Peetermans,Marijke, AU - Peeters,Miet, AU - Van Steen,Kristel, AU - Hoylaerts,Marc F, AU - Declerck,Paul J, AU - Verhamme,Peter, AU - Gils,Ann, Y1 - 2014/08/20/ PY - 2014/04/17/received PY - 2014/06/23/revised PY - 2014/08/04/accepted PY - 2014/9/7/entrez PY - 2014/9/7/pubmed PY - 2015/7/21/medline KW - Fibrinolysis KW - PAI-1 KW - Sensitivity and specificity KW - TAFI KW - Venous Thromboembolism SP - 1097 EP - 102 JF - Thrombosis research JO - Thromb Res VL - 134 IS - 5 N2 - 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. SN - 1879-2472 UR - https://www.unboundmedicine.com/medline/citation/25193405/Active_PAI_1_as_marker_for_venous_thromboembolism:_case_control_study_using_a_comprehensive_panel_of_PAI_1_and_TAFI_assays_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-3848(14)00440-X DB - PRIME DP - Unbound Medicine ER -