Relation of Intraperitoneal and Intravascular Coagulation and Fibrinolysis Related Antigens in Peritoneal Dialysis

1990 ◽  
Vol 63 (03) ◽  
pp. 356-360 ◽  
Author(s):  
E Gries ◽  
J Kopp ◽  
U Thomae ◽  
H Kuhlmann

SummaryPatients received 2,000 ml of dialysate intraperitoneally with five exchanges per day during continuous peritoneal dialysis (CAPD) for the treatment of terminal renal insufficiency. During a dwell time of 4 h the dialysate reached a total protein concentration up to 100 mg/dl by mass transfer of intravascular proteins. The composition is dependent on the molecular weight of the proteins. This results in an intraperitoneal hemostatic system of low concentration and different composition.We found an intraperitoneal fibrinogen cleavage and thrombin- antithrombin Ill-complex formation leading to increased levels of fibrinopeptide A (FPA: 33.3 ± 7.0 ng/ml) and thrombin-antithrombin Ill-complex (TAT: 4.7 ± 0.4 ng/ml) in plasma by mass transfer from dialysate to plasma. t-PA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) concentrations in plasma were within the normal range. The dialysate concentrations indicated a low local secretion. The fibrinolytic fibrin fragment D-dimer and the fibrinogen degradation product concentrations in plasma were greater than in dialysate. But the relations of the proteins between plasma and dialysate refer to a local intraperitoneal production as well.The results show that intraperitoneal coagulation predominates over fibrinolysis which is accompanied by an intravascular fibrinolysis in patients undergoing CAPD. Neoantigens produced in dialysate and diffused to plasma are comparable to changes seen in disseminated intravascular coagulation.

Author(s):  
Tae Ito ◽  
Yuko Suzuki ◽  
Hideto Sano ◽  
Naoki Honkura ◽  
Francis J Castellino ◽  
...  

Background: Details of the molecular interaction between tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) remain unknown. Methods and Results: Three distinct forms of high molecular weight complexes are demonstrated. Two of the forms were detected by mass spectrometry. The high molecular mass detected by MALDI-TOF MS spectrometry was 107,029 Da, which corresponds to the sum of molecular masses of the intact tPA (65,320 Da) and the intact PAI-1 (42,416 Da). The lower molecular mass was 104,367 Da and is proposed to lack the C-terminal bait peptide of PAI-1 (calculated mass, 3,804 Da) which was detected as a 3,808 Da fragment. When the complex was analyzed by SDS-PAGE, only a single band was observed. However, after treatment by SDS and Triton X-100, two distinct forms of the complex with different mobilities were shown by SDS-PAGE. The higher molecular weight band demonstrated specific tPA activity on fibrin autography, whereas the lower molecular weight band did not. Peptide sequence analysis of these two bands, however, unexpectedly revealed the existence of the C-terminal cleavage peptide in both bands and its amount was less in the upper band. In the upper band, the sequences corresponding to the regions at the interface between two molecules in its Michaelis intermediate were diminished. Thus, these two bands corresponded to distinct nonacyl-enzyme complexes, wherein only the upper band liberated free tPA under the conditions employed. Conclusion: These data suggest that under physiological conditions a fraction of the tPA-PAI-1 population exists as non-acylated-enzyme inhibitor complex.


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