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)

Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive
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PMID:Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XIa). 23 89

A study was carried out on mechanisms, independent of activated Factor XI, capable of activating Factor IX. The reaction product of tissue factor and Factor VII functioned as a potent Factor IX activator in the assay system used. Activated Factor IX itself activated Factor X; thrombin failed to activate Factor IX. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis confirmed that the reaction product of tissue factor and Factor VII activated Factor IX, with replacement of the band corresponding to native factor IX [molecular weight (Mr) 55,000] by bands corresponding to the heavy chain (Mr 27,000) and light chain (Mr 17,000) of activated Factor IX. When either Factor VII or calcium ions were left out of incubation mixtures, the band of native Factor IX persisted unchanged. Contact of blood with tissue factor represents a second mechanism, bypassing activated Factor XI, for the activation of Factor IX during hemostasis. It may help to explain the discrepancy between the mild bleeding of hereditary Factor XI deficiency and the severe bleeding of hereditary Factor IX deficiency.
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PMID:Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. 27 51

Plasma exchange has been proposed as a treatment for multiple disorders. Three patients with amyotropic lateral sclerosis, who were hemostatically normal, were studied through a total of 11 4-liter exchanges. Plasma was replaced by an equal volume of 5% albumin or 5% plasma protein fraction. Serial studies revealed that immediately after the exchange transfusion, there was significant prolongation of the prothrombin, partial thromboplastin, and thrombin times with reduction of the fibrinogen and antithrombin III levels. Factors V, VII-X, IX, and X were all significantly decreased, as were the factor VIII antigen, procoagulant, and the ristocetin cofactor activities. Platelet counts were obtained before and after exchanges and revealed significant decreases. Four hours after exchange, all parameters remained abnormal except the factor IX, ristocetin cofactor, and factor VIII procoagulant activities. By 24 hr, all hemostatic parameters had returned to normal. These studies indicate that plasma-exchange transfusion with material devoid of coagulation factors results in a coagulation defect that may be of clinical significance in a hemostatically compromised patient.
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PMID:The hemostatic imbalance of plasma-exchange transfusion. 46 36

The precise quantitation of activated factors in human factor IX concentrates has been accomplished with the use of recently developed, specific assays for factors IXa, Xa, and thrombin. The assay for factor IXa, which measures the initial rate of 3H-factor-X activation, was shown to be specific for factor IXa in the concentrates. Activated factor IX concentrates contained 1.0-2.3 microgram/ml of factor IXa; whereas the assays of unactivated concentrates were negative (less than 0.2 microgram/ml). The assays of factor Xa and thrombin, which measure the initial rate of p-nitroaniline release from S-2222 and S-2238, respectively, showed similar small amounts of factor Xa (4-34 ng/ml) and thrombin (12-76 ng/ml) in the activated and unactivated concentrates. The nonactivated partial thromboplastin time of the concentrates correlated significantly with the factor IXa content, but not with factor Xa or thrombin. Antithrombin III antigen in 3 of 4 concentrates was several-fold higher than antithrombin III activity, suggesting the presence of antithrombin III complexed with activated factors. These results support the hypothesis that the degree of activation of factor IX concentrates is related primarily to the concentration of factor IXa, which may be responsible for the thrombogenicity of these concentrates in some clinical settings.
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PMID:Activated clotting factors in factor IX concentrates. 49 95

Thrombin first activates and then inactivates factor VIII and for this reason thrombin has been considered responsible for the inactivation of factor VIII which occurs during clotting. Experiments described in this paper indicated that the activity of factor VIII is not reduced in factor IX or factor X deficient sera, while on the other hand this factor becomes inactivated in blood anticoagulated with high concentrations of hirudin which inhibit thrombin activity completely. This suggests that some other factor, besides thrombin, which is generated only in trace amounts in factor IX or factor X deficient plasmas, is also able to inactivate factor VIII. Purified factor X activated with insolubilized trypsin was added to purified preparations of factor VIII, which were free of both fibrinogen and prothrombin. Factor X a was allowed to act for 5-60 minutes and then inactivated with phenylmethanesulfonyl fluoride. Depending on the duration of the action of factor X a partial or complete inactivation of factor VIII was observed. This inactivation was also observed in the presence of hirudin, thus excluding the possibility that the effect was due to contamination with trace amounts of thrombin.
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PMID:Inactivation of factor VIII by a mechanism independent of the generation of thrombin. 50 1

The effect of collagen on isolated platelets, platelet-rich plasma and whole blood has been studied. Collagen failed to generate factor XIa-like activity in mixtures of isolated platelets, collagen and Ca++. Moreover, collagen added to whole blood or platelet-rich plasma containing 125I-factor IX and Ca++, also failed to form cleaved (activated) factor IX. In preliminary studies, lysed endothelial cells were found to enhance the formation of factor Xa and thrombin and to induce cleavage of 125I-factor IX in normal plasma, factor XII and factor-XI-deficient plasma even in the presence of antibody to tissue factor.
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PMID:The role of endothelial cells and subendothelial components in the initiation of blood coagulation. 51 Oct 12

Previous work from this department, concerned with testing the potential thrombogenicity of therapeutic factor IX concentrates, demonstrated that following recalcification of factor IX concentrates thrombin was generated within 3--30 minutes of incubation (Sas el al. 1975). The test developed (known as the TGt 50 test) is a two-stage assay and was thus found to be time consuming, tedious and tended to become inaccurate with long incubation periods and a large number of samples. A semiautomatic version of the test is reported in which the synthetic peptide Bz-ILE-GLU-GLY-ARG-pNA (S-2222) is added to recalcified, diluted factor IX concentrate in the micro-cuvette of a multiple sample recording spectrophotometer. Information can be obtained on (a) the amount of Xa (if any) present prior to recalcification (b) the initial amount of Xa formed and (c) the time taken to activate all factor =X to Xa. Direct graphical interpretation shows a number of qualitative differences between commercial preparations, but by either of the criteria (b) or (c) above, it is possible to place the different products into "activated" and "non activated" groups such that both the Xa generation times and TGt 50 tests identify the same two groups of products. This aggreement also indicates that the TGt 50 test is independent of the intrinsic factor V levels in the various concentrates.
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PMID:Spectrophotometric determination of factor Xa generation in factor IX concentrates. 57 33

Thrombogenicity of the factor IX concentrate and its clinical use for stoppage of the bleeding in the case of hemophilia A with inhibitor were reported. (1) Factor IX concentrate contained the coagulation factors as prothrombin complex (factors II, VII, IX and X); Thrombin and factor Xa. (2) Prothrombin in the factor IX concentrate could be converted to thrombin without any additional procoagulant such as thromboplastin or factor V, but in just 2.5M glycine solution by the effect of factor Xa. (3) The infusion of factor IX concentrate into a rabbit induced DIC promptly which was proved by autopsy and coagulation-fibrinolytic studies. (4) Factor IX concentrate showed a great efficacy in stopping the bleeding in the case of hemophilia A with inhibitor.
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PMID:Characteristics and thrombogenicity of factor IX concentrate. 61 88

Factor IX concentrate was obtained using DEAE-Sephadex A-50 as an adsorbent. The yield of factor IX in vitro averaged 81%. Each bottle of the concentrate contained 288-512 u. of factor II, 96--360 u. of factor VII, 440--660 u. of factor IX and 256--680 u. of factor X. The results of studies showed trace amounts of factor Xa in the final product, in the range of 0.01--0.04 u/ml. The concentrate was found to be free of thrombin. In the years 1976--1977 the new concentrate was administered 48 times to 10 patients with severe haemophilia B. The in vivo recovery of factor IX was 27--65%. Clinical results of treatment were satisfactory in all patients. No significant changes were observed in platelet count, fibrinogen level and the concentration of fibrinogen degradation products after infusion of the concentrate. The ethanol gelation test was negative in all cases.
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PMID:[Preparation and clinical use of a new factor IX concentrate]. 66 30

Having observed a marked increase of the fibrinopeptide A (FPA) level in vivo in 5 patients after the administration of factor IX concentrates, 8 factor IX concentrates (IX-K) and one FEIBA (factor eight inhibitor bypassing activity) fraction have been studied in vitro to ascertain whether thrombin was present or could be generated. Using fibrinogen as a substrate, the release of FPA under various conditions was measured by radioimmunoassay and it was found that (1) the addition of CaCl2 to the IX-K was necessary to produce FPA release; (2) the reaction was mainly dependent on the incubation time of the concentrate and the CaCl2 and (3) the release of FPA could be inhibited by heparin. The FEIBA fraction instantly produced FPA with or without the presence of CaCl2. It is therefore questioned whether the main effect of such products is due to a "factor II bypassing activity", i.e. thrombin.
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PMID:[Thrombin formation in factor IX concentrates and FEIBA (factor eight inhibitor bypassing activity) (proceedings)]. 69 97


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