SYSTEMIC CLOTTING ACTIVATION BY LOW-GRADE ENDOTOXEMIA IN LIVER-CIRRHOSIS - A POTENTIAL ROLE FOR ENDOTHELIA PROCOAGULANT ACTIVATION

Background. The pathophysiologic mechanism underlying the association between endotoxaemia and darting activation in liver cirrhosis is stil l to be explained. Aims. To investigate the relationship between endot oxaemia, endothelial perturbation and clotting system activation in li ver cirrhosis patients. Patients. The study was carried out in 30 cons ecutive patients (17 males, 13 females, age range 42 to 71 years) with liver cirrhosis. Methods. Prothrombin fragment F1+2, endotoxaemia, vo n Willebrand factor and ristocetin cofactor activity were studied in a ll patients. Von Willebrand factor antigen release and tissue factor e xpression were also evaluated in cultured endothelial cells incubated with low endotoxin concentrations (125-500 pg/ml).Results, Thirteen (4 3%) out of 30 liver cirrhosis patients showing von Willebrand factor a ntigen levels > 157 IU/dl (mean +/- 2SD of controls) were considered t o have signs of endothelial perturbation; they had more severe liver f ailure (p=0.0001), higher ristocetin cofactor activity (p=0.0001), end otoxin (p=0.0001) and prothrombin fragment F1+2 (p=0.0001) plasma valu es than liver cirrhosis with normal von Willebrand factor antigen. A s trong correlation (r = 0.97; p=0.0001) was found between prothrombin f ragment F1+2 and von Willebrand factor antigen. In in vitro experiment s endotoxin induced a concentration-dependent release of von Willebran d factor antigen (p=0.0001) an expression of tissue factor activity (p =0.0001) and antigen (p=0.0001) from cultured endothelial cells. Concl usions, This study suggests that the endothelial procoagulant activati on induced by low-grade endotoxaemia may represent a trigger for syste mic clotting activation in liver cirrhosis patients.