Liver cirrhosis is associated with alterations of the coagulation system commonly causing bleeding as well as thromboembolic complications. The potential pathophysiological roles of tissue factor (TF) (the initiator of the extrinsic coagulation pathway) and thrombomodulin (TM) (an initiator of the anticoagulatory protein C pathway) are unknown. We therefore measured plasma concentrations of TF and TM in 111 patients with liver diseases who were evaluated for liver transplantation. We could demonstrate that the levels of both molecules increased with the Child's class of liver cirrhosis, independently of aetiology. TM was significantly elevated in Child A, B and C patients compared with patients without cirrhosis; TF only in Child C patients. The plasma TM and TF concentrations correlated with prothrombin time, activated partial thromboplastin time, and inversely with factor VII activity, cholinesterase serum activity, and serum albumin concentration. TM was elevated in patients with a bleeding tendency, but TM and TF did not differ between patients with or without prior thrombotic events. Further studies are warranted to clarify the underlying mechanisms that raise TM and TF plasma levels in liver disease with possible clinical consequences. (C) 2001 Lippincott Williams & Wilkins.