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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Hyperfibrinolysis in alcoholic cirrhosis: Relative plasminogen activator inhibitor type 1 deficiency
Thrombosis Research, Volume 121, No. 5, Year 2008
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Description
Background: Over activity of the fibrinolytic system (hyperfibrinolysis) occurs in cirrhosis and has been shown to correlate with the risk of variceal hemorrhage. We have developed a model for assessing acute tissue plasminogen activator (t-PA) release in vivo in man. The aims of the study were to assess the contribution of basal and stimulated t-PA release to hyperfibrinolysis in patients with alcoholic cirrhosis. Methods: Bilateral forearm blood flow and plasma fibrinolytic variables were measured in 8 patients with biopsy proven alcohol induced cirrhosis, ascites and portal hypertension, and 8 age and sex matched healthy controls during infusion of bradykinin (100-900 pmol/min; endothelium-dependent vasodilator that releases t-PA) followed by sodium nitroprusside (SNP 2-8 μg/min; a control endothelium-independent vasodilator). Results: Baseline plasma t-PA antigen concentrations were higher in patients (14 ± 2 vs 9 ± 1 ng/mL; p < 0.05) whereas plasma plasminogen activator inhibitor type-1 (PAI-1) antigen concentrations were similar (59 ± 16 vs 55 ± 11 ng/mL; p = NS). This resulted in an increased t-PA activity (3 ± 1 vs 0 ± 0 IU/mL; p < 0.05) and reduced PAI-1 activity (9 ± 2 vs 21 ± 2 AU/mL; p < 0.05) indicating a relative deficiency of PAI-1 in patients with cirrhosis. Bradykinin and SNP caused dose-dependent vasodilatation (p < 0.001 for both) that did not differ between the two groups. Bradykinin caused a similar release of t-PA antigen (p < 0.05 for both) in both patients and controls (24 ± 17 vs 23 ± 7 ng/100 mL/min; p = ns) without affecting PAI-1 concentrations. Local t-PA activity was increased in patients following acute stimulated t-PA release (5 ± 1 vs 3 ± 1 IU/mL; p < 0.05). SNP caused no significant change in fibrinolytic parameters. Conclusion: Patients with alcoholic cirrhosis have a higher basal plasma t-PA activity because of a failure to increase plasma concentrations of its inhibitor, PAI-1. Furthermore, despite releasing normal amounts of t-PA acutely, higher t-PA activity remained due to the relative deficiency of PAI-1. This suggests that the pathogenesis of hyperfibrinolysis in alcoholic cirrhosis is the result of a relative PAI-1 deficiency and enhanced basal t-PA release. © 2007 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Ferguson, James W.
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Helmy, Ahmed
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Ludlam, Christopher A.
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Hayes, Peter Clive
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Newby, David Ernest
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Statistics
Citations: 24
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1016/j.thromres.2007.07.008
ISSN:
00493848
Research Areas
Noncommunicable Diseases
Substance Abuse