Plasma from patients with cirrhosis increases tissue plasminogen activator release from vascular endothelial cells in...

In patients with severe liver disease, blood levels of many coagulation and fibrinolytic factors are lowered due to a diminished synthetic capability in the liver. Tissue plasminogen activator (t-PA) is synthesized by the vascular endothelial cells, however, and is increased in such patients.

Amounts of t-PA secreted were determined by immunosorbent assay after plasma from patients with cirrhosis was added to cultured human umbilical vein endothelial cells to determine whether a plasma factor directly enhanced t-PA secretion from vascular endothelial cells.

Release of t-PA was significantly higher with exposure to plasma from patients with decompensated cirrhosis than when plasma from patients with compensated cirrhosis or normal subjects was used (p < 0.01 and p < 0.05, respectively). Plasminogen activator inhibitor 1 (PAI-1) concentrations were measured similarly but did not differ among the three groups.

Our results indicate that factors in plasma from patients with decompensated cirrhosis directly stimulate t-PA release from the vascular endothelial cells, while any increased PAI-1 release observed in comparable in vivo situations is probably an indirect response to an increase of t-PA or a result of impaired hepatic clearance.