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PubMed1987

Increased thromboplastic potential in diabetes: a multifactorial phenomenon.

Coagulation parameters, platelet aggregation, and thromboxane production as well as metabolic parameters were measured in 31 diabetic patients, 12 without and 19 with clinically manifest late complications, and in 14 healthy control subjects. Spontaneous in vitro aggregation as well as ADP, collagen, and arachidonic acid induced aggregation were higher in both groups of diabetic patients, without an increase in thromboxane B2 production. In diabetic patients with late complications an increase in fibrinogen, fibrinogen cyanogen bromide peptide, factor VIII related antigen, C1-esterase inhibitor, and antithrombin III was observed in comparison to healthy subjects. Fibrinogen, C1-esterase inhibitor, and factor VIII related antigen were already elevated in diabetic patients without clinically manifest late vascular complications. No strict correlations were found between serum glucose, glycosylated hemoglobin, and glycosylated albumin, on the one hand, and coagulation promoting or inhibiting factors, aggregation or thromboxane B2 production, on the other, in either control or diabetic subjects. Also no correlations existed between the coagulation parameters and the aggregation results. In vitro incubation of pooled normal plasma with different glucose concentrations had no influence on the methods by which the coagulation parameters were measured. These data indicate that rather early in the diabetic state many changes take place in different phases of the thrombostatic process, all resulting in an increased hemostatic diathesis.

Adult↗

PubMedDate not supplied

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

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. Beta 2-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 micrograms/mL), and the fibrinolysis markers DD (851 +/- 26 ng/mL), FbDP (1.0 +/- 0.3 microgram/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 (beta 2-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 +/- 3.2 micrograms/L), FbDP (16.4 +/- 2.9 micrograms/L), 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.

Acute Disease↗