IMBALANCE BETWEEN INTRAPERITONEAL COAGULATION AND FIBRINOLYSIS DURINGPERITONITIS OF CAPD PATIENTS - THE ROLE OF MESOTHELIAL CELLS

We compared peritoneal dialysis effluents from 18 CAPD patients who ha d not suffered from peritonitis during the last 6 months (group 1) wit h the effluents from five patients with acute peritonitis (group 2), m easuring activation markers of coagulation and fibrinolysis. These mar kers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrom bin III complex (TAT), fibrin monomer (FM), and fibrin degradation pro ducts (FbDP). In the dialysate of group 1 we found remarkably high lev els of F1 + 2, TAT and FM concomitant with a high concentration of FbD P, indicating a high rate of intraperitoneal fibrin turnover. The bala nce between peritoneal generation and degradation of fibrin was distur bed in untreated patients of group 2, who had significantly higher lev els of coagulation markers and a higher ratio between FM and FbDP. Sev en days after treatment with intraperitoneal administration of antibio tics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fi brin turnover we investigated the expression of tissue-type plasminoge n activator (t-PA), urokinase-type plasminogen activator (u-PA), plasm inogen activator inhibitor type-1 (PAl-1), and tissue factor in cultur ed human peritoneal MC under basal conditions and after exposure to tu mour necrosis factor alpha (TNF alpha), interleukin-1 alpha(IL- 1 alph a), or bacterial lipopoly-saccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolyt ic activity by decreasing t-PA production and increasing PAI-1 synthes is. Furthermore the addition of TNF alpha resulted in activation of th e coagulation cascade by the expression of tissue factor. These in-vit ro findings explain the imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients.