Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis.
OBJECTIVE
The bleeding tendency of patients suffering from cirrhosis is in part ascribed to accelerated fibrinolysis. In this study, the role of the recently discovered inhibitor of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI) in cirrhosis was examined.


METHODS
In 64 patients with cirrhosis of varying severity, TAFI antigen levels were measured by enzyme-linked immunosorbent assay and compared with TAFI levels in control subjects. Furthermore, a plasma-based fibrinolysis assay was performed in the presence and absence of a specific inhibitor of activated TAFI.


RESULTS
TAFI levels were decreased in cirrhosis. Mean TAFI levels were 66% in Child's A, 55% in Child's B, 47% in Child's C cirrhosis, and 26% in acute liver failure. Decreased TAFI antigen levels were highly correlated with antithrombin and alpha(2)-antiplasmin activity levels. Clot lysis times and clot lysis ratio (defined as ratio between clot lysis time in the absence and presence of a specific inhibitor of activated TAFI) of cirrhotics were not significantly different from healthy controls.


CONCLUSIONS
Despite decreased levels of TAFI and other components of the fibrinolytic system, no evidence of increased plasma fibrinolytic potential in cirrhosis is observed using the plasma-based assay of this study. The reduction of antifibrinolytic factors in cirrhosis is compensated by the concomitant reduction in profibrinolytics.
Lisman
T
T
Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, 3508 GA Utrecht, The Netherlands. j.a.lisman@lab.azu.nl
Leebeek
F W
FW
Mosnier
L O
LO
Bouma
B N
BN
Meijers
J C
JC
Janssen
H L
HL
Nieuwenhuis
H K
HK
De Groot
P G
PG
D000941:Antigens / Q000097:blood; D000991:Antithrombins / Q000378:metabolism / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D025901:Carboxypeptidase B2; D002268:Carboxypeptidases / Q000172:deficiency* / Q000494:pharmacology*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000145:classification / Q000276:immunology; D013997:Time Factors
D000941:Antigens; D000991:Antithrombins; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2