THE FIBRINOLYTIC SYSTEM IN HUMAN ASCITES

Background: We recently reported that the contact and kallikrein-kinin systems are activated in malignancy-related ascites. We have now studied the fibrinolytic system in ascites and plasma from patients with gastrointestinal cancer (n = 14) and non-malignant liver disease (n = 18). Methods and Results: Enzyme immunoassays (EIAs) showed that urokinase and tissue plasminogen activators (uPA, tPA) and PA inhibitors (PAI-1, PAI-2) were present in ascites from both patient groups and that tPA was the predominant PA. uPA, tPA, and PAI-1, but not PAI-2, were detected in plasma from patients and controls. These EIA findings were supported by zymography studies. Functional assays showed considerable generation of plasmin-like activity and low plasminogen and antiplasmin values in malignancy-related ascites. The plasmin/antiplasmin and tPA/PAI-1 ratios were particularly high in malignancy-related ascites as compared with non-malignant ascites. Plasma from the liver disease patients showed a higher tPA/PAI-1 ratio and, thus, a higher potential for plasminogen activation than plasma from cancer patients and controls. Patient plasma showed low values of plasmin-like activity, antiplasmin, and plasminogen. Conclusion: Our findings show that the fibrinolytic system is activated in malignancy-related ascites.