Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrinopeptides were measured as direct indices of thrombin, plasmin and elastase in plasma samples obtained from patients with AML. Peptide patterns observed were consistent with spontaneous or drug induced plasmin-specific fibrinogenolysis (AML FAB M 1/3), elastase mediated proteolysis (AML FAB M 3/4) or DIC (AML FAB 4/5). DIC was also observed in septic, agranulocytotic patients.
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PMID:Fibrinogen--proteolysis in acute myelogenous leukemia (AML). 294 Oct 88

The inhibitory effect of gabexate mesylate, which is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation, and as a regional anticoagulant agent for hemodialysis, has been measured on bovine factor Xa, bovine alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, human urokinase, porcine pancreatic beta-kallikrein-B, and bovine beta-trypsin catalyzed hydrolysis of p-nitrophenyl esters of N-alpha-carbobenzoxy-L-arginine and N-alpha-carbobenzoxy-L-lysine. On the basis of enzyme:gabexate mesylate affinities, the serine proteases can be arranged as follows: human urinary kallikrein approximately porcine pancreatic beta-kallikrein-B much less than bovine beta-trypsin approximately bovine factor Xa approximately human Lys77-plasmin approximately human urokinase approximately bovine alpha-thrombin. The mode of binding of gabexate mesylate to the serine proteases conforms to the active-reactive site geometries observed in their complexes with natural and synthetic inhibitors. Differences in gabexate mesylate affinities for these proteases reflect structural differences at their primary specificity subsite, which have been investigated by comparative analysis of amino acid sequences and by computer-graphics techniques.
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PMID:Gabexate mesylate inhibition of serine proteases: thermodynamic and computer-graphics analysis. 310 78

Levels of alpha 2PI-plasmin complex and tissue-type plasminogen activator (t-PA) in plasma were determined in 10 cases of acute promyelocytic leukemia (APL) with marked coagulopathy and in 10 cases of hematological malignancies with DIC to investigate relevance to fibrinolysis. In the both groups, levels of alpha 2PI-plasmin complex increased and were inversely proportional to levels of fibrinogen and alpha 2PI. Levels of t-PA in plasma increased moderately in the majority of the both groups. Serial observation of the concentrations of t-PA with corresponding changes in the levels of fibrinogen, alpha 2PI, alpha 2PI-plasmin complex and FDP could not demonstrate any significant relationship between levels of t-PA and the other parameters. From these results, it is unlikely that levels of t-PA in plasma directly influence on the degree of consumption of alpha 2PI or of formation of alpha 2PI-plasmin complex in most cases of DIC.
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PMID:Changes in levels of t-PA and alpha 2PI-plasmin complex in plasma in patients with DIC. 314 64

A detailed review of the dynamic processes of coagulation and fibrinolysis precedes a discussion of clinical applications, especially for users of oral contraception and others with antithrombin-III disorders. Coagulation and fibrinolysis are both initiated by activation of circulating pro-enzymes, namely thrombin and plasmin. Both of these have circulating and local inhibitors that modify stages of the clotting and fibrinolytic processes. The circulating system, also called the intrinsic coagulation system, can be regarded as an amplification system related to the extrinsic, or cellular system. Antithrombin-III (AT-III) is a specific plasma protein that inhibits coagulation at the step (after platelets aggregate) of fibrin formation. At-III can be measured immunologically, or functionally by its ability to bind thrombin in the presence of heparin. Familial AT-III deficiencies incur a risk of venous thrombosis, and may be total or partial, depending on the type of genetic defect. Affected individuals may be treated with vitamin-K antagonists, anabolic steroids, or subcutaneous, low-dose heparin. Episodes of thrombosis may also represent acquired AT-III deficiency, such as in pregnancy, abortion, post-surgery, or disseminated intravascular coagulation. The approximately 10% decrease in AT-III seen in women taking estrogen-containing oral contraceptives is within normal limits. The oral route is significant, as AT-III is a protein made by the liver. This fall is not of any physiological significance, since the plasma euglobulin fibrinolytic system is also increased. Some pill users with AT-III deficiency or other thrombosis-prone conditions, however, may be at risk of increased thrombosis.
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PMID:Pathophysiology and clinical aspects of fibrinolysis and inhibition of coagulation. Experimental and clinical studies with special reference to women on oral contraceptives and selected groups of thrombosis prone patients. 327 96

The prognosis of septicaemia depends on the occurrence of complications such as shock and coagulation defects. The damage to haemostasis is usually explained by the action of the main coagulation and fibrinolysis enzymes, thrombin and plasmin. This paper presents data concerning the role of a third protease, granulocytic elastase. 82 patients who had been admitted to our hospital with suspected septicaemia were examined. Septicaemia was proven in 22 patients by the growth of microorganisms in blood cultures, and was clinically diagnosed in 9 patients. The plasma levels of neutrophil elastase-like protease complexed to a1antitrypsin (a1AT-ELP) were measured by zone immunoelectrophoresis assay (ZIA). The a1AT-ELP values were significantly increased in the 31 septic as compared to the 51 non-septic patients. In patients with complicated septicaemia, negative correlations of a1AT-ELP with factor XIII and the coagulation inhibitor antithrombin III were demonstrable. Among the patients with septic complications, the 3 who survived exhibited a dramatic decrease of a1AT-ELP, whereas in the other 16 patients who died the levels remained elevated. It might be of therapeutic significance that in 9 patients receiving fresh plasma and AT III-concentrate substitution for DIC the a1AT-ELP levels dropped, whereas they remained high in the other septicaemia patients. There were no correlations between a1AT-ELP and the a2antiplasmin-plasmin complexes (a2AP-P1), but strong correlations with signs of coagulation. The data suggest an interaction of coagulation and elastase release, probably involving the Hageman factor.
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PMID:Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections. 329 74

Monoclonal antibodies (mabs) were raised against X-oligomers, the earliest soluble fragments released from crosslinked fibrin (XL-FN), by the action of plasmin. Two of the mabs (NIBn 52 and NIBn 123) were monospecific for X-oligomers in that they showed no binding to fibrinogen, the plasmic fragments of fibrinogen (D and E) and non-crosslinked fibrin (X, Y, D and E), or the terminal digestion product of XL-FN, fragment DD-E. One other mab (NIBn 178) was panspecific for X-oligomers in that it exhibited a weak affinity for fibrinogen. The mabs were used to develop a two-site immunoradiometric assay (IRMA) and an enzyme-linked immunospecific assay (ELISA) which permitted the specific measurement of X-oligomers directly in plasma, rather than in serum. This immunoassay is a true assay of fibrinolysis as distinct from fibrinogenolysis and may be a potential aid in the diagnosis and evaluation of thrombosis. In preliminary studies, the assay detected low levels of X-oligomers in normal plasma and elevated levels in patients with disseminated intravascular coagulation.
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PMID:Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). I. Characterization and preliminary evaluation in plasma. 334 97

Distribution analyzing latex immunoassay (DALIA), a sensitive method based on the agglutination of latex particles coated with monoclonal antibody, was developed for determination of fibrin degradation products (FDP) in human plasma. The agglutination is measured by using an electric particle counter designed for medical research to determine the volume-ratio of agglutinated to non-agglutinated particles. Interference by serum constituents is avoided by coating the particles with the F(ab')2 fragments of monoclonal antibody and by using suitable latex particles. This assay enabled the determination of FDP in concentrations of 16 to 4000 ng/ml in less than 15 minutes. The mean concentrations of FDP in the plasma of 98 normal subjects and 142 patients with apparent disseminated intravascular coagulation (DIC) were 0.69 and 13.24 micrograms/ml, respectively. Analytical recovery of FDP in plasma samples averaged 104%. The correlation coefficient of DALIA with enzyme immunoassay using two monoclonal antibodies, was 0.809. The results obtained by analyzing the cross-reactivity with related components of FDP and the inhibitory effect of D monomer indicated that the present method can effectively detect the high molecular weight (HMW) fragments of FDP produced in the early stage of plasmin digestion.
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PMID:Determination of FDP in human plasma by a novel latex immunoassay. 341 15

In several diseases, such as disseminated intravascular coagulation, fibrin-fibrinogen degradation products (FDP) can be detected when serum is used. To avoid the use of serum with the risk of falsely positive and negative results, and to quantitatively measure routinely low levels of FDP in plasma, we developed a solid-phase enzyme immunoassay (EIA), using a monoclonal antibody (No. FDP-14). It reacts specifically with FDP, but not with the parent fibrinogen-fibrin molecule. To raise the monoclonal antibodies we injected into mice a whole mixture of fibrin degradation products isolated after complete lysis of a human blood clot by tissue-type plasminogen activator, because there is a chance that such products resemble FDP in patients' blood more closely than antigens derived from purified fibrinogen. The EIA developed is a two-step assay ("cap-tag procedure"), in which the monoclonal antibody is attached to the wells of microtiter plates. The monoclonal antibody is specific for a neoantigenic determinant in the fragment E moiety, exposed after degradation of fibrinogen-fibrin by plasmin. The assay discriminates neither between degradation products of fibrinogen and fibrin nor between fibrin degradation products that are or are not cross-linked. It is not disturbed by the presence of fibrinogen or fibrin monomer in plasma. The assay is accurate above 60 ng FDP per milliliter and has a detection limit down to approximately 10 ng FDP per milliliter when the supernatant of a lysed blood clot is used as calibration material. In frozen, then thawed plasma specimens from normal individuals, FDP values varied between 30 and 110 ng/ml. Plasma of patients with disseminated intravascular coagulation and of patients receiving thrombolytic therapy had increased FDP values. In patients with ovarian carcinoma, FDP concentrations in plasma varied with the clinical course of the disease. Results indicate that the EIA for FDP in plasma is promising as a diagnostic tool in different clinical situations.
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PMID:New enzyme immunoassay of fibrin-fibrinogen degradation products in plasma using a monoclonal antibody. 354 Jan 64

Numerous investigators have postulated that a hypercoagulable state exists in humans for a period of time before the development of thrombotic episodes. A clear biochemical definition of the prethrombotic state, however, has proved elusive due in part to the lack of reliable techniques for monitoring pertinent changes in blood coagulability. Based on recent advances in our knowledge of the biochemistry of the coagulation system, a series of highly sensitive and specific immunochemical tools has been developed that can quantitate the activities of various steps of the hemostatic mechanism in vivo at the subnanomolar level. We have established assays for F1+2 and the protein C activation peptide, which measure the cleavage of the prothrombin molecule by factor Xa and the scission of protein C by the thrombin-thrombomodulin complex, respectively. Nossel and coworkers had previously constructed similar assays for fibrinopeptide A (FPA) and fragment B beta 1-42, which monitor the cleavage of fibrinogen by thrombin and the proteolysis of fibrin I by plasmin, respectively. Substantial elevations in the levels of these markers have been found in patients with disseminated intravascular coagulation and many subjects with acute deep venous thrombosis. The F1+2 and FPA assays have been used to demonstrate that significant increments in factor Xa activity but not thrombin activity regularly occur in the blood of nonanticoagulated individuals with congenital deficiencies of antithrombin or protein C. These two disorders are known to be correlated with the subsequent development of thrombosis. Patients with protein C deficiency have also been noted to have significantly reduced plasma levels of protein C activation peptide. By using the immunoassays for FPA and B beta 1-42 in studies of postoperative patients, it has been shown that an imbalance between the procoagulant action of thrombin and the anticoagulant effect of plasmin on fibrin I polymer may induce an acquired thrombotic diathesis. Finally, we have recently demonstrated that prothrombin activation as measured by the F1+2 assay is suppressed by oral anticoagulants in the blood of patients with thrombotic diatheses. These investigations suggest that these assay techniques can be used to improve our understanding of the hypercoagulable state as well as to develop more effective treatment strategies for the prevention of thromboembolic events.
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PMID:The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. 360 75

Hypofibrinogenemia and disseminated intravascular coagulation are common events in patients with metastatic prostate carcinoma. This study tests the hypothesis that prostate tumor growth and metastasis is associated with sustained activation of fibrinolysis secondary to increased release of plasminogen activator. We implanted an androgen-insensitive prostate tumor into an inbred strain of rats and serially measured plasminogen, plasminogen activator, plasmin and fibrinogen. Control groups included animals without tumor and a group implanted with transitional cell bladder carcinoma, a locally infiltrating tumor not usually associated with hemostatic complications. Our results showed a significant and steady rise in plasma plasminogen activator, plasmin and fibrinogen levels in animals implanted with prostate cancer. This, however, is not specific for prostate tumor. Similar, perhaps more profound changes were noted in animals implanted with the transitional cell carcinoma.
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PMID:The fibrinolytic system in experimental prostate tumor. 381 May 52


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