Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells |
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Authors: | Sitter T; Spannagl M; Schiffl H; Held E; van Hinsbergh V W M; Kooistra T |
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Institution: | 1Medizinische Klinik, Klinikum Innenstadt, University of Munich Germany
2Gaubius Laboratory TNO-PG Leiden, The Netherlands |
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Abstract: | We compared peritoneal dialysis effluents from 18 CAPD patientswho had not suffered from peritonitis during the last 6 months(group 1) with the effluents from five patients with acute peritonitis(group 2), measuring activation markers of coagulation and fibrinolysis.These markers included prothrombin fragment F1+2 (F1+2), thrombin-antithrombinIII complex (TAT), fibrin monomer (FM), and fibrin degradationproducts (FbDP). In the dialysate of group 1 we found remarkablyhigh levels of F1+2, TAT and FM concomitant with a high concentrationof FbDP, indicating a high rate of intraperitoneal fibrin turnover.The balance between peritoneal generation and degradation offibrin was disturbed in untreated patients of group 2, who hadsignificantly higher levels of coagulation markers and a higherratio between FM and FbDP. Seven days after treatment with intraperitonealadministration of antibiotics and heparin, F1+2, TAT, FM andFbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritonealfibrin turnover we investigated the expression of tissue-typeplasminogen activator (t-PA), urokinase-type plasminogen activator(u-PA), plasminogen activator inhibitor type-1 (PAI-1), andtissue factor in cultured human peritoneal MC under basal conditionsand after exposure to tumour necrosis factor (TNF ) interleukin-1 (IL-1 ), or bacterial lipopolysaccharide (LPS). The exposureof MC to TNF or to a lesser extent IL-1 or LPS reduced theirfibrinolytic activity by decreasing t-PA production and increasingPAI-1 synthesis. Furthermore the addition of TNF resulted inactivation of the coagulation cascade by the expression of tissuefactor. These in-vitro findings explain the imbalance betweenintraperitoneal coagulation and fibrinolysis during peritonitisof CAPD patients. |
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Keywords: | continuous ambulatory peritoneal dialysis (CAPD) intraperitoneal fibrinolysis mesothelial cells peritonitis |
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