Systemic clotting activation by low-grade endotoxaemia in liver cirrhosis: a potential role for endothelial procoagulant activation.
BACKGROUND
The pathophysiologic mechanism underlying the association between endotoxaemia and clotting activation in liver cirrhosis is still to be explained.


OBJECTIVE
To investigate the relationship between endotoxaemia, endothelial perturbation and clotting system activation in liver cirrhosis patients.


METHODS
The study was carried out in 30 consecutive patients (17 males, 13 females, age range 42 to 71 years) with liver cirrhosis.


METHODS
Prothrombin fragment F1 + 2, endotoxaemia, von Willebrand factor and ristocetin cofactor activity were studied in all patients. Von Willebrand factor antigen release and tissue factor expression were also evaluated in cultured endothelial cells incubated with low endotoxin concentrations (125-500 pg/ml).


RESULTS
Thirteen (43%) out of 30 liver cirrhosis patients showing von Willebrand factor antigen levels > 157 IU/dl (mean +/- 2SD of controls) were considered to have signs of endothelial perturbation; they had more severe liver failure (p = 0.0001), higher ristocetin cofactor activity (p = 0.0001), endotoxin (p = 0.0001) and prothrombin fragment F1 + 2 (p = 0.0001) plasma values than liver cirrhosis with normal von Willebrand factor antigen. A strong correlation (r = 0.97; p = 0.0001) was found between prothrombin fragment F1 + 2 and von Willebrand factor antigen. In in vitro experiments endotoxin induced a concentration-dependent release of von Willebrand factor antigen (p = 0.0001) and expression of tissue factor activity (p = 0.0001) and antigen (p = 0.0001) from cultured endothelial cells.


CONCLUSIONS
This study suggests that the endothelial procoagulant activation induced by low-grade endotoxaemia may represent a trigger for systemic clotting activation in liver cirrhosis patients.
Ferro
D
D
Institute of Clinical Medicine I, University of Rome La Sapienza, Italy.
Basili
S
S
Lattuada
A
A
Mantovani
B
B
Bellomo
A
A
Mannucci
P M
PM
Violi
F
F
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D019446:Endotoxemia / Q000097:blood* / Q000150:complications; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D014841:von Willebrand Factor; D011516:Prothrombin; D013925:Thromboplastin