A shift in balance between profibrinolytic and antifibrinolytic factors causes enhanced fibrinolysis in cirrhosis

Frank W.G. Leebeek*, Cornelis Kluft, Eduard A.R. Knot, Moniek P.M. De Maat, J. H.Paul Wilson

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

114 Citations (Scopus)

Abstract

The aim of this study was to assess the cause of enhanced fibrinolysis in cirrhosis by studying the balance between profibrinolytic and antifibrinolytic proteins in 24 patients with mild or severe cirrhosis. Antigen levels of both tissue-type plasminogen activator and plasminogen-activator inhibitor 1 were increased in mild and severe cirrhosis. Activity levels showed a very wide variability, but median activity levels of both proteins were normal. In most patients, the increase in tissue-type plasminogen activator was counterbalanced by the increased levels of plasminogen-activator inhibitor 1, but in a subgroup of patients the change in balance resulted in extremely high tissue-type plasminogen-activator levels. The specific activity of both proteins (activity/ antigen quotient) was reduced in either mild or severe cirrhosis. This finding indicates either that more enzyme-inhibitor complexes circulate in the blood of patients with cirrhosis than in normal individuals or that dysfunctional molecules circulate. Plasminogen and α2-antiplasmin antigen and activity levels were decreased in both mild and severe cirrhosis. The binding of α2-antiplasmin to fibrin was decreased in severe cirrhosis, making fibrin clots more susceptible to lysis. Clot lysis experiments were performed to see if equal decreases in plasminogen and α2-antiplasmin levels, as found in cirrhosis, result in a change in the rate of fibrinolysis. It was found that the proportionate decreases led to enhancement of fibrinolysis, indicating that the inhibitor depletion is more important than the proenzyme depletion. The authors conclude that enhanced fibrinolysis frequently found in cirrhosis may be attributed to an increased tissuetype plasminogen-activator activity relative to plasminogen-activator-inhibitor activity and decreased levels of α2-antiplasmin, resulting in a reduced binding of α2-antiplasmin to fibrin.

Original languageEnglish
Pages (from-to)1382-1390
Number of pages9
JournalGastroenterology
Volume101
Issue number5
DOIs
Publication statusPublished - Nov 1991

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