Fibrinolytic proteins in human bile accelerate lysis of plasma clots and induce breakdown of fibrin sealants.
OBJECTIVE
We investigated the effect of human bile on the stability of plasma clots and of fibrin sealants.


BACKGROUND
Fibrin sealants are extensively used in liver surgery, for example, during liver resections. Although these sealants have been developed to induce hemostasis, in practice these products are actually mainly used to seal dissected bile ducts to prevent postsurgical bile leakage.


METHODS
We performed in vitro assays in which clotting and lysis of human plasma clots or fibrin sealants was studied in presence or absence of human bile.


RESULTS
Addition of bile to human plasma resulted in a dose-dependent increase in clotting time, and a dose-dependent decrease in clot lysis time. Bile also accelerated lysis of in vitro clotted fibrin sealants. Immunodepletion of tissue-type plasminogen activator (tPA) resulted in partial depletion of the lysis promoting activity of bile. Immunodepletion of both tPA and lysine-binding proteins from bile fully abolished the lytic activity, suggesting that tPA and plasminogen present in human bile are responsible for the lysis-promoting effect. Surprisingly, addition of high dose plasminogen activator inhibitor type 1 (PAI-1) to bile did not attenuate the lytic activity toward fibrin sealants, which suggested that tPA in a biliary environment may be unsusceptible to PAI-1 inhibition. Indeed, bile acids were shown to prevent tPA from interacting with PAI-1, although preformed complexes were not destabilized upon addition of bile acids.


CONCLUSIONS
These combined results suggest that the presence of tPA and other fibrinolytic proteins in human bile results in lysis of plasma clots or fibrin sealants, which potentially could affect the efficacy of the latter products.
Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Elizabeth A
EA
Boonstra
Jelle
J
Adelmeijer
Henkjan J
HJ
Verkade
Marieke T
MT
de Boer
Robert J
RJ
Porte
Ton
T
Lisman
D001646:Bile / Q000737:chemistry* / Q000502:physiology*; D001777:Blood Coagulation / Q000502:physiology*; D015718:Fibrin Tissue Adhesive / Q000737:chemistry*; D005342:Fibrinolysis / Q000502:physiology*; D006488:Hemostasis, Surgical; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000502:physiology
D015718:Fibrin Tissue Adhesive; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors