Abstract

Background—Previous studies have shown that cirrhotic patients produce 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 to Child-Pugh criteria.

Methods—Prothrombin fragment F1+2, monocyte TF 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). Monocytes from cirrhotic patients had higher TF activity and antigen than those from controls (p<0.001) with a progressive increase from low to severe liver failure. Monocyte expression of TF was significantly correlated with plasma levels of F1+2 (TF activity:r=0.98, p<0.0001; TF antigen:r=0.95, p<0.0001) and with endotoxaemia (TF activity: r=0.94, p<0.0001; TF antigen:r=0.91, p<0.0001). PCR analysis of TF mRNA showed TF expression only in three patients with endotoxaemia (more than 15 pg/ml).

Conclusions—Cirrhotic patients have enhanced expression of TF which could be responsible for clotting activation, suggesting that endotoxaemia might play a pivotal role.