Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the clinical significance of two novel assays for the detection of crosslinked fibrin degradation products (XDP) in whole blood using the agglutination of the red blood cells (SimpliRED D dimer and SimpliRED D dimer-500, AGEN, Australia). XDP made serially by plasmin in vitro, were detected by the SimpliRED D dimer assay, but fibrinogen degradation products showed weak reactivity. Ten of the fifty four clinical samples collected with EDTA-2K, changed to positive on these assays after overnight incubation at 4 degrees C. Anemia and hemolytic samples had no effect on the assay results. The results obtained by the SimpliRED D dimer were negative for the normal subjects (n = 50) without exception. In our study, 81% and 95% of the patients, who showed abnormal levels of XDP in plasma and E fragments in serum respectively, were positive on the SimpliRED D dimer assay. The assay was as sensitive as the Rapidia-D dimer assay. In conclusion, the SimpliRED D dimer assay was clinically useful as a screening assay for the diagnosis of hypercoagulable and fibrinolytic states, since it could be performed simply and quickly.
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PMID:[Evaluation of novel assays for the detection of crosslinked fibrin degradation products in whole blood by the agglutination of the red blood cells]. 130 33

Although the possible occurrence of systemic fibrinogenolysis has been suggested in patients with metastasising prostatic cancer (MPC), direct evidence is lacking. We report on a patient with MPC whose laboratory data were consistent with hyperfibrinolysis: marked decrease of alpha 2-antiplasmin (AP) level (less than 50% of normal), increase of plasmin-alpha 2-antiplasmin complex, D-fragment of fibrin and fibrinogen degradation products [FDP(D)] and cross-linked fibrin degradation products (XDP). The patient neither showed laboratory nor clinical evidence for consumption coagulopathy except for a slight increase in thrombin-antithrombin III complex level. Immunoblotting of the patient's serum using an anti-fibrinogen antibody revealed the presence of a 250 kDa protein in addition to DD fragments. Following reduction of this protein by 2-mercaptoethanol after extraction from SDS-PAGE gel, gamma-chain of fibrinogen (47 kDa) was found by immunoblotting using a monoclonal antibody recognising a 86-302 residue of the gamma-remnant of fibrinogen. Moreover, the 250 kDa protein did not bind to Sepharose 4B to which a monoclonal antibody recognising the N-terminus of fragment D was conjugated. These findings indicated that this protein was not fragment DY, but rather fibrinogen fragment X. With the retraction of the prostatic tumour by an effective therapy, the patient's AP level increased gradually. When the plasma AP level rose to 60% of normal, the fragment X was no longer detectable. These findings suggested that systemic fibrinogenolysis occurred in the patient with MPC only when AP levels were markedly decreased.
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PMID:Direct evidence for systemic fibrinogenolysis in a patient with metastatic prostatic cancer. 151 30

The aim of this study was to evaluate the type of enzymes involved in tumor-associated fibrinolysis of the stroma component fibrin in ovarian cancer patients. For this purpose, the high-molecular-mass fibrin degradation products (HMM-XDP) were isolated from malignant ascitic fluid by protamine sulfate precipitation and further purified by gel filtration and acid precipitation. After reduction with 2-mercaptoethanol, the peptide chain components were separated by reverse-phase high-performance liquid chromatography (RP-HPLC). The nature of these components was elucidated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and N-terminal amino acid sequence analysis and compared with fibrin-derived fragments formed in vitro. The results indicate that plasmin is the essential protease involved in the degradation of the stroma-derived fibrin portion found in ovarian cancer ascites.
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PMID:Role of plasmin in the degradation of the stroma-derived fibrin in human ovarian carcinoma. 213 49

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.
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PMID:Thrombin and plasmin generation in patients with liver disease. 252 2

Plasma levels of alpha 2-plasmin inhibitor (alpha 2PI), plasmin-alpha 2PI complex and cross-linked fibrin derivatives (XDP) were measured in 8 patients (12 episodes) with thromboembolic disorders on the initial administration of urokinase. In conjunction with a decrease in plasma alpha 2PI activity and antigen, plasmin-alpha 2PI complex increased following urokinase infusion in all cases except one who received a low dose (60,000 units) of urokinase. However, changes in XDP were variable among the patients. Plasma XDP level increased markedly in one, moderately in 4, slightly in one, and remained unchanged in 6 cases (episodes). The increment of plasma XDP correlated (r = 0.804, p = 0.003) with the dose of urokinase administered, but was independent of changes in plasmin-alpha 2PI complex. The plasma XDP elevation was associated with clinical improvement. These results suggest that simultaneous measurements of XDP and plasmin-alpha 2PI complex in plasma would be valuable for the pharmacological or hemostatic assessment of thrombolytic therapy.
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PMID:Evaluation of fibrinolytic therapy by measuring cross-linked fibrin derivatives and plasmin-alpha 2-plasmin inhibitor complex in plasma. 296 45

Blood samples from patients with suspected pulmonary embolism (PE) were obtained at the time of diagnostic lung scanning to determine whether identification of those with activation of endogenous fibrinolytic pathways could serve as a screening test for PE. Cross-linked fibrin degradation products (XDPs) were measured by a quantitative enzyme-linked immunoassay with a specific monoclonal antibody (MabCO Dimertest EIA) that recognizes cross-linked D-dimer fragments and related high molecular weight fibrin derivatives containing D-dimer but that does not cross-react with fibrinogen or its plasmin degradation products. PE was present in 19 with positive pulmonary angiograms and absent in 50 with completely normal lung scans. Elevated levels of XDPs (greater than 144 ng/ml) were present in 17 of 19 patients (89%) with PE and in 28 of 50 (56%) without PE (p = 0.30). Among those with PE present, the XDP levels were (means +/- sd) 864 +/- 1,068 ng/ml (median = 470 ng/ml) compared with 285 +/- 395 ng/ml (median = 155 ng/ml) among those with PE absent (p = 0.003). For PE detection, elevated XDP levels provided a sensitivity of 89%, a specificity of 44%, a positive predictive value of 38%, a negative predictive value of 92%, and an accuracy of 57%. Among those with elevated XDP levels and PE absent, 75% had no apparent reason for XDP elevations. These data indicate that XDPs are significantly elevated in patients with PE but that, in contrast to earlier reports, measurement of XDPs among individuals with suspected PE may not be sufficiently accurate to be clinically useful in screening.
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PMID:Utility of cross-linked fibrin degradation products in the diagnosis of pulmonary embolism. 340 May 69

To investigate the relationship between changes in plasma concentrations of polymorphonuclear elastase (PMN-E) and haemostatic effects during haemodialysis (HD), changes in the plasma concentrations of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and fibrinogen (Fbg), cross-linked fibrin degradation products (XDP), thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC) and soluble thrombomodulin (TM) in 49 patients with end-stage chronic glomerulonephritis maintained on chronic HD were measured. Plasma concentrations of TAT, PIC, TM and E-alpha 1 PI significantly increased during a single HD. There was a statistically significant correlation between change in plasma E-alpha 1 PI concentration and changes in plasma concentrations of TAT, PIC and TM during a single HD, as well as between changes in plasma concentrations of TM and TAT during a single HD. These observations suggested that activation of coagulation and fibrinolysis, endothelial cell damage, and activation of polymorphonuclear cells occur during HD. Activation of polymorphonuclear cells may induce activation of coagulation and fibrinolysis, leading to endothelial cell damage, augmented by release of proteases such as elastase.
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PMID:Relationship between elevation in the plasma concentration of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and haemostatic parameters during haemodialysis. 779 53

We measured plasma levels of soluble fibrin (SF) in 98 patients suspected of having disseminated intravascular coagulation (DIC) using a newly developed enzyme-linked immunosorbent assay (ELISA) and investigated the correlations between SF determinations and measurements of other hemostatic molecular markers to determine the diagnostic usefulness of determinations of SF. Patients were classified into four groups according to their clinical and laboratory findings: overt DIC (n =33), subclinical DIC (n =23) hypercoagulability (n =22), and non-DIC (n =20). SF levels were significantly higher in patients with overt DIC compared with the other three groups and were significantly higher in the subclinical DIC and hypercoagulability groups compared with the non-DIC patients. SF levels increased significantly with each increase in the clinical stage. Although levels of thrombin-antithrombin III complex (TAT), prothrombin fragment 1 + 2 (PF 1+2), cross-linked fibrin degradation products (XDP), and plasmin-antiplasmin complex (PAP) were significantly increased in patients with overt DIC compared with non-DIC patients, the values of these hemostatic molecular markers did not consistently show an increase in association with advances in the disease stage. Plasma levels of SF in patients with overt DIC showed a positive correlation with levels of TAT, XDP,and FDP(E), but not with PF1+2 and PAP. Analysis of receiver-operating characteristic curves showed that the sensitivity and specificity of SF were similar to those of XDP for diagnosis of DIC. The sensitivity and specificity of SF for diagnosis of overt DIC were both above 90% when the cut-off value was set at 65 mu g/ml.plasma levels of SF were also increased in patients with extravascular fibrin formation without DIC. Our findings suggest that measurement of plasma levels of SF by this ELISA method is useful for the diagnosis of DIC and the evaluation of the patient's clinical status.
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PMID:Determination of plasma soluble fibrin using a new ELISA method in patients with disseminated intravascular coagulation. 861 98

Recently, a new fibrinogen/fibrin degradation products(FDP) test using monoclonal antibodies against FDP(LPIA FDP-P: FDP-P) has been developed, which is able to measure FDP directly in plasma. The objective of this study is to clarify clinical significance of the test in the diagnosis of fibrinogenolysis and fibrinolysis in comparison with a conventional FDP test using polyclonal antibodies against fibrinogen(FDP-S) and D-dimer test using monoclonal antibodies against D-dimer(D-D). The monoclonal antibodies used in FDP-P test was shown to recognize fragment X, Y and D1 derived from fibrinogen digested by urokinase, and was also to recognize XDP fragments, D-dimer and D derived from cross-linked fibrin digested by tissue plasminogen activator using SDS-PAGE and immunoblotting analysis. There was a good correlation of FDP levels between FDP-P test and FDP-S test. However, levels of FDP in both tests were discrepant in several samples. There was a tendency that the levels of FDP were higher in FDP-S test than in FDP-P test. Such discrepancy was suggesting that soluble fibrin monomer complex(FM) was recognized by the antibodies used in FDP-S test, but not recognized by the antibodies used in FDP-P test. There was also a good correlation of FDP levels between FDP-P test and D-D test. However, the levels of FDP in both tests were discrepant in several samples. The levels of FDP were higher in FDP-P test than in D-D test. These discrepant samples had lower levels of antiplasmin and higher levels of plasmin antiplasmin complex(PIC), and also showed XDP fragments, D-dimer, X, Y, and D1 by using SDS-PAGE. These observations suggest that D-D test measures only fibrinolytic fragments, while FDP-P test measures fibrinogenolytic fragments as well as fibrinolysis. In results, the FDP-P test was confirmed to be a useful tool to examine fibrinogenolysis as well as fibrinolysis more specifically than the conventional FDP test.
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PMID:[Clinical significance of a new fibrinogen/fibrin degradation products(FDP) test using plasma samples for the diagnosis of fibrinogenolysis and fibrinolysis]. 1130 30

Plasma levels of granulocyte-derived elastase (GE-XDP), D-dimer, and soluble fibrin (SF) were examined in 177 patients with disseminated intravascular coagulation (DIC) of various etiologies. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with sepsis and solid cancer. The ratio of GE-XDP/ D-dimer was significantly high in patients with trauma, burn, and sepsis, suggesting that fibrinolysis due to GE-XDP may be dominant in DIC. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with overt DIC and correlated with DIC score. Plasma levels of GE-XDP, but not SF, correlated significantly with D-dimer. Plasma levels of D-dimer, but not SF, correlated significantly with plasmin plasmin inhibitor complex (PPIC). Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in nonsurvivors. Plasma levels of GE-XDP, but not SF, correlated significantly with sepsis-related organ failure assessment (SOFA) score. These results suggest that GE-XDP is a potentially useful marker for the diagnosis of overt-DIC and as a predictor of organ failure-related outcome.
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PMID:Elevated plasma levels of fibrin degradation products by granulocyte-derived elastase in patients with disseminated intravascular coagulation. 1624 64


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