Coagulation and fibrinolysis-related antigens in plasma and dialysate of CAPD patients

Abstract

Objective: The present study is aimed at gaining insight into coagulation and fibrinolysis in the peritoneal cavity of patients on continuous ambulatory peritoneal dialysis (CAPD). For this purpose we measured coagulation- and fibrinolysis-related antigens in plasma and dialysate, comparing patients with and without peritonitis. Design: Markers of activated coagulation and fibrinolysis in plasma and dialysate of CAPD patients were determined at different time points (0 hr, 2 hr, 4 hr) after infusion of the dialysis solution in the peritoneal cavity. Prothrombin fragment (F1+2), thrombin-antithrombin III complex (TAT), and fibrin monomer (FM) were chosen as parameters of activated coagulation. Fibrin degradation products (FbDP), D-dimer (DD), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) were measured as parameters for ongoing fibrinolysis. Beta2-microglobulin, albumin, and IgG were used as marker proteins for the diffusion of proteins of intravascular origin into the peritoneal cavity. Patients: Eleven clinically stable CAPD patients, who had not suffered from peritonitis during the last six months, and 5 CAPD patients with an acute episode of bacterial peritonitis were studied. Results: In the dialysate of stable CAPD patients (n = 11) the concentration of activation markers of coagulation and fibrinolysis increased continuously with dwell time. After four hours we found remarkably high levels of the coagulation markers F1+2 (0.4 ± 0.1 nmol/L), TAT (6.5 ± 1.0 ng/mL), and FM (24.5 ± 7.1 μg/ml), and the fibrinolysis markers DD (851 ± 26 ng/mL), FbDP ± 1.0 ± 0.3 μg/mL), t-PA (3.3 ± 0.8 ng/mL), and PAI-1 (2.6 ± 1.2 ng/mL). The dialysate-to-plasma (D/P) ratios of all of these antigens were significantly higher compared to the D/P ratios of proteins with similar molecular weight, which are not produced intraperitoneally (β2-microglobulin, albumin, and IgG). These findings point to a local, thrombin-induced intraperitoneal fibrin generation during regular CAPD. Compared with clinically stable CAPD patients, the patients with bacterial peritonitis (n = 5) had significantly higher levels of F1+2 (5.3 ± 1.6 nmol/L), TAT (57.8 ± 10.7 ng/ml), FM (972 ± 302 μg/mL), FbDP (16.4 ± 2.9 μg/mL), and PAI-1 (7.3 ± 2.4 ng/mL) in the dialysate (4-hr dwell time), and a 2.4-times higher ratio between FM and FbDP. These results can be interpreted as an intraperitoneal imbalance between coagulation and fibrinolysis during peritonitis. Conclusion: Our study demonstrates a high intraperitoneal fibrin formation, not only during peritonitis but also in clinically stable CAPD patients. The remarkably high levels of coagulation (F1+2, TAT, FM) and fibrinolysis (FbDP, DD, t-PA, PAI-1) related antigens in the dialysate of patients without peritonitis cannot be explained by transport from plasma into the peritoneal cavity and may reflect a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin is obviously disturbed in CAPD patients with peritonitis, who had significantly higher levels of coagulation markers in the dialysate and a higher ratio between FM and FbDP.