COAGULATION-RELATED AND FIBRINOLYSIS-RELATED ANTIGENS IN PLASMA AND DIALYSATE OF CAPD PATIENTS

Objective: The present study is aimed at gaining insight into coagulat ion and fibrinolysis in the peritoneal cavity of patients on continuou s 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. Prot hrombin 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 plasmi nogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI -1) were measured as parameters for ongoing fibrinolysis. Beta(2)-micr oglobulin, albumin, and IgG were used as marker proteins for the diffu sion of proteins of intravascular origin into the peritoneal cavity. P atients: 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 th e dialysate of stable CAPD patients (n = 11) the concentration of acti vation markers of coagulation and fibrinolysis increased continuously with dwell time. After four hours we found remarkably high levels of t he coagulation markers F1 + 2 (0.4 +/- 0.1 nmol/L), TAT (6.5 +/- 1.0 n g/mL), and FM (24.5 +/- 7.1 mu g/mL), and the fibrinolysis markers Do (851 +/- 26 ng/mL), FbDP (1.0 +/- 0.3 mu g/mL), t-PA (3.3 +/- 0.8 ng/ mt), and PAI-1 (2.6 +/- 1.2 ng/mL). The dialysate-to-plasma (D/P) rati os of all of these antigens were significantly higher compared to the D/P ratios of proteins with similar molecular weight, which are not pr oduced intraperitoneally (beta(2)- microglobulin, albumin, and IgG). T hese findings point to a local, thrombin-induced intraperitoneal fibri n generation during regular CAPD. Compared with clinically stable CAPD patients, the patients with bacterial peritonitis (n = 5) had signifi cantly higher levels of F1 + 2 (5.3 +/- 1.6 nmol/L), TAT (57.8 +/- 10. 7 ng/mL), FM (972 +/- 302 mu g/ml), FbDP (16.4 +/- 2.9 mu g/mL), and P AI-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 interpre ted as an intraperitoneal imbalance between coagulation and fibrinolys is during peritonitis. Conclusion: Our study demonstrates a high intra peritoneal fibrin formation, not only during peritonitis but also in c linically stable CAPD patients. The remarkably high levels of coagulat ion (F1+2, TAT, FM) and fibrinolysis (FbDP, Do, t-PA, PAI-1) related a ntigens in the dialysate of patients without peritonitis cannot be exp lained by transport from plasma into the peritoneal cavity and may ref lect a high rate of intraperitoneal fibrin turnover. The balance betwe en peritoneal generation and degradation of fibrin is obviously distur bed in CAPD patients with peritonitis, who had significantly higher le vels of coagulation markers in the dialysate and a higher ratio betwee n FM and FbDP.