ENHANCED EXPRESSION OF MONOCYTE TISSUE FACTOR IN PATIENTS WITH LIVER-CIRRHOSIS

Background - Previous studies have shown that cirrhotic patients produ ce increased amounts of thrombin but the underlying mechanism is still unknown. Aims - To analyse the relation between the rate of thrombin generation and monocyte expression of tissue factor (TF) in cirrhosis. Patients - Thirty three cirrhotic patients classified as having low ( n = 7), moderate (n = 17), or severe (n = 9) liver failure according t o Child-Pugh criteria. Methods - Prothrombin fragment F1+2, monocyte T F activity and antigen, and endotoxaemia were measured in all patients . Polymerase chain reaction (PCR) analysis of TF mRNA was performed in monocytes of five cirrhotic patients. Results - Prothrombin fragment F1+2 was higher in cirrhotic patients,than in controls (p < 0.0001). M onocytes from cirrhotic patients had higher TF activity and antigen th an those from controls (p < 0.001) with a progressive increase from lo w to severe liver failure. Monocyte expression of TF was significantly correlated with plasma levels of F1+2 (TF activity: r = 0.98, p < 0.0 001; TF antigen: r = 0.95, p < 0.0001) and with endotoxaemia (TF activ ity: r = 0.94, p < 0.0001; TF antigen: r = 0.91, p < 0.0001). PCR anal ysis of TF mRNA showed TF expression only in three patients with endot oxaemia (more than 15 pg/ml). Conclusions - Cirrhotic patients have en hanced expression of TF which could be responsible for clotting activa tion, suggesting that endotoxaemia might play a pivotal role.