TAFI deficiency in liver cirrhosis: relation with plasma fibrinolysis and survival.
BACKGROUND
TAFI (thrombin-activatable fibrinolysis inhibitor) is a potent anti-fibrinolytic and anti-inflammatory factor of liver origin. It is markedly reduced in liver cirrhosis but its effect on fibrinolysis remains controversial and no data are available on its prognostic value. We evaluated the relationship of TAFI level with plasma fibrinolysis and survival in cirrhotic patients.


METHODS
Sixty-five patients with liver cirrhosis were studied. TAFI antigen, plasma fibrinolysis and other laboratory variables were assayed at study entry and their association with mortality was assessed during a 3-year follow-up.


RESULTS
TAFI level and fibrinolysis time were markedly reduced in liver cirrhosis as compared to healthy subjects (p<0.0001) and TAFI deficiency was strongly correlated with fibrinolysis time (p=0.0002). TAFI level at entry, but not fibrinolysis time, was significantly lower in non-survivors (n=25) than in survivors (n=40, p=0.0001). By Cox regression analysis, after adjustment for possible confounding factors, TAFI, but not fibrinolysis time, was identified as an independent predictor of mortality. TAFI assay, moreover, showed a clinically relevant accuracy in assessing patients' survival (ROC curve analysis, p<0.0001) achieving a sensitivity of 92%, a specificity of 55%, and a negative predictive value of 91.7%.


CONCLUSIONS
Our data indicate that TAFI deficiency in liver cirrhosis is associated with enhanced plasma fibrinolysis. Moreover, they suggest that TAFI, but not fibrinolysis time, is a strong predictor of survival and thus TAFI assay might prove useful to select candidates for liver transplantation.
Gresele
Paolo
P
Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy. grespa@unipg.it
Binetti
Bianca M
BM
Branca
Giovanna
G
Clerici
Carlo
C
Asciutti
Stefania
S
Morelli
Antonio
A
Semeraro
Nicola
N
Colucci
Mario
M
D025901:Carboxypeptidase B2 / Q000097:blood / Q000172:deficiency*; D005260:Female; D005342:Fibrinolysis; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013997:Time Factors
D025901:Carboxypeptidase B2