Cited by 245Blood Coagulation and Thrombosis MechanismsProtease and Inhibitor MechanismsCoagulation, Bradykinin, Polyphosphates, and Angioedema

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Clearance of Tissue Plasminogen Activator (TPA) and TPA/Plasminogen Activator Inhibitor Type 1 (PAI-1) Complex: Relationship to Elevated TPA Antigen in Patients With High PAI-1 Activity Levels

Chandler, W. L., Alessi, M. C., Aillaud, M. F., Henderson, P., Vague, P., Juhan-Vague, I.·1997·Circulation

DOI 10.1161/01.cir.96.3.761

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Abstract

Background To evaluate the effect of plasminogen activator inhibitor type 1 (PAI-1) levels on the clearance of total tissue plasminogen activator (TPA) antigen, we studied the clearance of active TPA and TPA/PAI-1 complex in subjects with low (181±109 pmol/L; n=7) and high (1166±322 pmol/L; n=4) baseline active PAI-1. Methods and Results A 5-μg/kg bolus of TPA was infused over a 15-second period followed by measurement of TPA activity, TPA antigen, TPA/PAI-1, TPA/C1 inhibitor, PAI-1 activity, and PAI-1 antigen over a 4-hour period. α-Phase clearance of total TPA antigen was faster in subjects with low PAI-1 (t 1/2 of 3.5±0.7 minutes) versus high PAI-1 (t 1/2 of 5.3±0.9 minutes) ( P =.006). Clearance of all factors was best fit by a two-compartment pharmacokinetic model based on a computer-simulated human circulatory system. The average hepatic clearance fraction in the two-compartment model was greater for active TPA (89±10%, t 1/2 of 2.4±0.3 minutes) than for TPA/PAI-1 complex (48±17%, t 1/2 of 5.0±1.8 minutes) ( P =.0006). Conclusions Plasma clearance of active TPA was faster than clearance of TPA/PAI-1 complex. High levels of active PAI-1 converted more TPA into TPA/PAI-1 complex, effectively slowing the clearance of total TPA antigen and explaining in part why high levels of PAI-1 activity are associated with increases in total TPA antigen.

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10.1161/circ.92.10.2984 · DOI
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Authors: Chandler, W. L., Alessi, M. C., Aillaud, M. F., Henderson, P., Vague, P., & Juhan-Vague, I.
Affiliations: Inserm (FR)
ORCID: Chandler, W. L.
Alessi, M. C.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1997-08-05
Volume: 96
Issue: 3
Pages: 761-768
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.96.3.761
OpenAlex: W1998362943
Cited by: 245
References: 54
Citations by year: 2026: 6 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 9 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 14 · 2015: 5 · 2014: 8 · 2013: 9 · 2012: 6
FWCI: 6.72
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Health Sciences › Medicine › Hematology › Coagulation, Bradykinin, Polyphosphates, and Angioedema
Keywords: tissue plasminogen activator, plasminogen activator inhibitor-1, t-PA/PAI-1 complex, plasma clearance, pharmacokinetics, hepatic clearance, fibrinolysis, two-compartment model
MeSH terms: Adult, Antigens, Computer Simulation, Female, Humans, Male, Middle Aged, Models, Biological, Tissue Plasminogen Activator, Plasminogen Activator Inhibitor 1

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Clearance of Tissue Plasminogen Activator (TPA) and TPA/Plasminogen Activator Inhibitor Type 1 (PAI-1) Complex: Relationship to Elevated TPA Antigen in Patients With High PAI-1 Activity Levels

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