Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma.
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PMID:Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule. 20 86

Two new families of congenital dysfibrinogenemia originating from French Canada are reported. The dysfibrinogenemia in the first family is characterized by an abnormal aggregation of the fibrin monomers; the defect in the second family is due to a faulty release of fibrinopeptides during the proteolytic phase of the thrombin-fibrinogen reaction.
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PMID:[Fibrinogen Quebec I and Quebec II: two new families of dysfibrinogenemia (author's transl)]. 41 77

Abnormalities of fibrin formation were studied in 42 young adult patients with benign viral hepatitis. It was observed that there was a constant increase in thrombin time and reptilase time, evoking an abnormality of the second stage of fibrin formation, or the aggregation of fibrin monomers. This abnormality is not associated with the presence of inhibitors in the patients' serums, and is maximum at an alkaline pH. The hypothesis of an abnormality of the fibrinogen molecule, a dysfibrinogenemia, is the most likely cause, and this has to be confirmed by biochemical and immunochemical studies.
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PMID:[Abnormalities of fibrin formation in benign viral hepatitis (author's transl)]. 43 13

To evaluate the possibility that the carbohydrate composition of fibrinogen may be altered in the dysfibrinogenemia associated with liver disease, we studied the sialic acid content of purified fibrinogen from 12 patients with liver disease and its relationship to the prolongation of the thrombin time. Purified fibrinogen showed that Aalpha-, Bbeta-, and gamma-chains when reduced and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and exhibited prolongation of the thrombin time similar to that of the plasma from which it was derived. Sialic acid content of the purified fibrinogen ranged from 12.7 to 71.4% higher in patient fibrinogens when compared to normal controls. A progressive delay in thrombin time was associated with increasing sialic acid content of the patient fibrinogen. Enzymatic removal of sialic acid from four of the abnormal fibrinogens resulted in a shortening of their thrombin times to the range of the desialylated normal control. Periodic acid-Schiff reagent stained only the Bbeta- and gamma-chains of the reduced patient fibrinogens after sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the excess sialic acid is located on these two chains. These studies demonstrate a biochemical alteration of the functionally abnormal fibrinogen found in some patients with liver disease, and indicate that the excess sialic acid plays an important role in the functional defect of this protein.
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PMID:Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease. 62 Dec 88

A 14-yr-old girl Down syndrome developed a unique type of circulating inhibitor causing a mild bleeding tendency and interfering strongly with coagulation tests, including reptilase time, and with the reaction of purified fibrinogen and thrombin. The concentration of all coagulation factors was normal. The inhibitor had no direct effect on thrombin activity or on the aggregation of fibrin monomer in plasma. Chromatography on DEAE-cellulose and neutralization by immune sera revealed that the inhibitor was an immunoglobulin of IgG class with both kappa and lambda determinants. Isolated inhibitor delayed the release of fibrinopeptide A from a normal fibrinogen reacting with thrombin and retarded the onset of visible clotting, but had no effect on the the final degree of clottability. The clinical and laboratory features of this patient resemble those of patients with congenital dysfibrinogenemia associated with abnormal fibrinopeptide release.
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PMID:Acquired coagulation inhibitor delaying fibrinopeptide release. 75 15

A new case of congenital dysfibrinogenemia has been discovered in a 20 year old woman, who suffered from a severe postpartal hemorrhage after the delivery of her first child, followed by episodes of thrombosis. Coagulation studies reveal a prolongation of thrombin time, reptilase time was immeasurable. Thromboplastin time and partial thromboplastin time were slightly prolonged. Low fibrinogen levels were obtained by techniques, which depend on the coagulation velocity following addition of thrombin, while immunological procedures gave slightly diminished values of fibrinogen. Patients's fibrinogen had a moderate inhibitory effect on the fibrin formation in normal plasma. However, inhibitors of the fibrinogen-fibrin conversion could not be detected. Coagulation factors were normal, fibriolysis as well. The cause of the coagulation disorder was found to be a defect of the fibrinogen molecule, leading to an abnormal fibrin polmerization of patient's fibrin monomers. The release of the fibrinopeptides in the paperelectrophoresis was normal. The defect of the fibrinogen molecule did not protect from thrombotic complications. The same defect could be found in the lower scale in patient's father, 4 of her 7 brothers and sisters, and her son.
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PMID:Fibrinogen Marburg a new genetic variant of fibrinogen. 83 66

To test the possibility that a functionally abnormal fibrinogen may exist in some patients with liver disease, we studied the plasma and purified fibrinogens of five patients whose plasma thrombin times were prolonged at least 40% over normal controls. In no patient was there evidence of disseminated intravascular coagulation and/or fibrinolysis. No abnormalities were detected by immunoelectrophoresis of plasmas or purified fibrinogens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced patient fibrinogens showed normal mobility and amount of Aalpha, Bbeta, and gamma chains. Alkaline polyacrylamide gel electrophoresis and gradient elution, DEAE-cellulose chromatography of admixtures of radio-iodinated patient (125)I-fibrinogen and normal (131)I-fibrinogen showed identical mobility in the gel and simultaneous elution from the column, respectively. Thrombin and Reptilase (Abbott Scientific Products Div., Abbott Laboratories, South Pasadena, Calif.) times of purified patient fibrinogens were prolonged, and calcium ions improved but did not completely correct these defects. Increasing amounts of thrombin progressively shortened the clotting times of patient fibrinogens but not to the level of normal. Addition of equal amounts of patient fibrinogen to normal fibrinogen resulted in a prolongation of the thrombin time of the normal protein. Thrombin-induced fibrinopeptide release was normal. Fibrin monomers prepared from patient plasmas and purified fibrinogens demonstrated impaired aggregation at low (0.12) and high (0.24) ionic strength. These studies demonstrate that some patients with liver disease and prolonged plasma thrombin times have a dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization.
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PMID:Dysfibrinogenemia associated with liver disease. 87 92

A new case of dysfibrinogenemia is reported which shows no signs of a haermorrhagic diathesis (dysfibrinogenemia Giessen III). The abnormal fibrinogen was detected by only slight but characteristic alterations of some parameter of the coagulation analysis (prolonged clotting times after addition of thrombin, Reptilase and thrombin coagulase; low fibrinogen concentration determined by methods based on clot formation in comparison to the immunological fibrinogen determination; delayed fibrin polymerization). In addition, clinical features and diagnosis of dysfibrinogenemia are described in general.
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PMID:[Dysfibrinogenemia. A new case: dysfibrinogenemia Giessen III (author's transl)]. 88 74

Treatment of fibrinogen with maleic acid anhydride renders fibrinogen unclottable depending on the degree of modification of the molecule. According to radioactive studies the release of fibrinopeptides by thrombin or reptilase is undisturbed. The incoagulability is due to inhibition of the polymerization process of fibrinmonomers derived from modified fibronogen, mainly caused by the increase of electronegative charges upon the fibrogen molecule. According to discelectrophoretic analysis modified fibrinogen fails to produce fragments D and E following plasmic digestion, however, may be degraded to high molecular weight products. Modified fibrinogen reveals some similarities to abnormal fibrinogens in congenital dysfibrinogenemia with regard to its functional properties.
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PMID:Studies on chemically modified fibrinogen. 98 32

The subunit structure of fibrinogen Baltimore and fibrin formed from this inherited dysfibrinogenemia was analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The molecular weights of the alpha-, b- and gamma-chains of fibrinogen Baltimore were found to be identical to those of normal fibrinogen. Noncross-linked fibrin formed from both purified fibrinogen Baltimore as well as normal fibrinogen contained two alpha-monomers (alpha1 and alpha2). alpha2 was presumed to be alpha-monomer from which fibrinopeptide A had been released. The evolution of alpha2 during clotting of fibrinogen Baltimore was delayed and appeared to be quantitatively reduced when compared to normal. Crosslinked fibrin formed from fibrinogen Baltimore possessed an abnormal subunit structure. alpha-polymers were not generated in thrombin-induced, factor XIII-rich clots of fibrinogen Baltimore under conditions of pH and calcium concentration suitable for complete alpha-polymerization in normal fibrin. If clotting was carried out with calcium concentrations twice that required for normal clots or at pH 6.4, fibrin from fibrinogen Baltimore was completely cross-linked. These structural analyses of fibrin formed from fibrinogen Baltimore substantiate earlier findings that indicate a defect in the alpha-chain of this dysfibrinogenemia.
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PMID:Defective alpha-polymerization in the conversion of fibrinogen Baltimore to fibrin. 113 67


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