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)

Two thrombolytic agents are mainly used in patients: streptokinase (SK) and urokinase (UK). UK from human origin is an endopeptidase which is able to convert plasminogen into plasmin. UK is only secreted by the kidney and is only found in urine which is presently the only source of extraction. Studies in man have shown that UK produces a highly reproducible state of enhanced plasma thrombolytic activity with a high fibrinolysis/fibrnogenolysis ratio and a lack of toxicity and antigenicity. The half life in Animal is short as well as the duration of fibrinolytic activity in Man. In clinical experience, positive results have been reported in pulminary embolism while the issues in myocardial infarction are controversial. Suggestive results have been registered in deep vein thrombosis, in ophthalmologic field and in desobstruction of arterio-venious shunts. No evident benefit has been noted in cerebral vascular disease. Up to now, UK has been very well tolerated.
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PMID:[Urokinase. Biochemical therapeutical and therapeutical data (author's transl)]. 6 58

High molecular weight kininogen (HMW-kininogen) concentration was measured in the plasma of healthy blood donors, patients with haemophilia A, idiopathic thrombocytopoenic purpura, deep vein thrombosis treated with oral anticoagulants and patients treated with streptokinase (SK). The concentration of HMW-kininogen in the plasma of healthy subjects was 92 +/- 15 micrograms/ml. The values obtained in patients' plasma were not different statistically. In the plasma of patients treated with repeated infusion of SK, a significant increase of HMW-kininogen antigen activity was noted after each injection of the drug. Similar results were obtained when SK was added to plasma "in vitro" or when a purified preparation of HMW-kininogen was treated with plasmin. These and additional data obtained suggest that plasmin uncovers in the HMW-kininogen molecule a new antigenic site(s) common to HMW-kininogen and low molecular weight kininogen and new antigenic site(s) specific only for HMW-kininogen.
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PMID:Plasma high molecular weight kininogen concentration in health and in chosen impairments of haemostasis. Evidence that plasmin uncovers a new antigenic site in high molecular weight kininogen. 9 69

The fibrinolytic response of 12 patients receiving single daily infusions of 600,000 units of streptokinase (SK) and 90 mg of plasminogen for the treatment of DVT has been studied. The mean plasminogen concentration was maintained throughout the treatment period (4-6 days) at between 20-40% the initial value, while mean circulating plasmin concentration rose to only about twice initial plasma levels. The degradation of fibrinogen as indicated by a fall in clottable fibrinogen did not fall below 1 mg/ml and serum FDP rose to greater than 1 mg/ml. Limited fibrinogenolysis occurred in 2 patients, while in another patient who bled there was immediate and extensive depletion to below 0.5 mg/ml. The beneficial clinical results obtained with this regimen (Kakkar et al. 1975), which produces only limited systemic plasminaemia, suggest that thrombolysis may be facilitated by higher levels of plasminogen than those maintained during conventional SK treatment.
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PMID:Intermittent plasminogen-streptokinase treatment of deep vein thrombosis. 13 63

This review deals with aspects of fibrinolysis in which significant developments have taken place in the last few years. The structural changes of plasminogen during its activation are now identified precisely; the recent description of a thrombotic tendency in a kindred characterized by a defect of this protein emphasizes its important role in the homeostatic balance. Several activators of plasminogen are now identified; some of them, such as tissue and vascular activators, appear to have an important role in physiology and pathology. The recent characterizations of the alpha 2-antiplasmin and of antiactivators have widened our understanding of the inhibitors of fibrinolysis: a defect of the plasmin inhibitor seems to be associated with an haemorrhagic tendency, whereas high antiactivator levels were encountered in thrombotic conditions. The clinical use of fibrinolytic agents appears to be promising in conditions such as recurrent deep vein thrombosis and in the post-phlebitic syndrome. Thrombolytic therapy with urokinase or streptokinase appears to have elective indications in patients with acute deep vein thrombosis and massive life-threatening pulmonary embolism.
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PMID:Progress in fibrinolysis. 16 15

Lower rates of deep vein thrombosis have been noted following total hip replacement under epidural anesthesia in patients receiving exogenous epinephrine throughout surgery. To determine whether this is due to enhanced fibrinolysis or to circulatory effects of epinephrine, 30 patients scheduled for primary total hip replacement under epidural anesthesia were randomly assigned to receive intravenous infusions of either low dose epinephrine or phenylephrine intraoperatively. All patients received lumbar epidural anesthesia with induced hypotension and were monitored with radial artery and pulmonary artery catheters. Patients receiving low dose epinephrine infusion had maintenance of heart rate and cardiac index whereas both heart rate and cardiac index declined significantly throughout surgery in patients receiving phenylephrine (p = 0.0001 and p = 0.0001, respectively). Tissue plasminogen activator (t-PA) activity increased significantly during surgery (p < 0.005) and declined below baseline postoperatively (p < 0.005) in both groups. Low dose epinephrine was not associated with any additional augmentation of fibrinolytic activity perioperatively. There were no significant differences in changes in D-Dimer, t-PA antigen, alpha 2-plasmin inhibitor-plasmin complexes or thrombin-antithrombin III complexes perioperatively between groups receiving low dose epinephrine or phenylephrine. The reduction in deep vein thrombosis rate with low dose epinephrine is more likely mediated by a circulatory mechanism than by augmentation of fibrinolysis.
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PMID:The hemodynamic and fibrinolytic response to low dose epinephrine and phenylephrine infusions during total hip replacement under epidural anesthesia. 144 77

Forty-one patients who had all participated in studies about prophylaxis of postoperative deep venous thrombosis (DVT) were investigated 5-8 years after operation. Twenty-five had had asymptomatic DVT detected by 125I-fibrinogen uptake test or 99mTc plasmin scintigraphy and verified by phlebography, four of which were bilateral. They received anticoagulant treatment for three months. Sixteen patients had normal screening tests. At the follow up legs in which DVT had previously been diagnosed were compared with normal legs in patients who did not have DVT. There was no significant difference in subjective symptoms between the two groups of legs, although there were more complaints of oedema and restlessness in legs in which DVT had been diagnosed and varicose veins were more common. When the incidence of varicose veins before the operation and at the follow up was compared, more patients who had had a DVT had developed varicose veins. Blood volume and venous refilling time were measured by strain gauge plethysmography, and were significantly lower in those with a history of DVT than in normal legs. The results indicate impaired venous function in patients who previously had had asymptomatic DVT treated with anticoagulants.
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PMID:Late complications of asymptomatic deep venous thrombosis. 168 76

In this review, an attempt has been made to present new data on the mechanisms that can be involved in DVT and to emphasize the role of the cell in these processes. It has been demonstrated that cells can mediate the relevant expression of tissue factor without cell disruption and that the fibrinolytic responses can also be modulated by the cells. It has also been demonstrated that the fibrinolytic system seems to be designed to work on the cell surface based upon (1) the existence of specific receptors, (2) the modulation of the expression of these receptors and (3) the comprehensive increase in plasmin generation by up-regulating, for example, the plasminogen receptors. It could also be worthwhile to attempt to explain some beneficial effects of drugs such as heparins by studying their action on these compartments. It is important to note that recently Rosenfeld et al. have described an increase in t-PA and u-PA binding to endothelium by pre-incubation of endothelial cells with unfractionated heparin. This work would be a first step in a very exciting and interesting new era in the prevention of venous thromboembolism.
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PMID:Biochemical aspects of the pathogenesis of venous thrombosis. 228 80

Plasma levels of betathromboglobulin (BTG), fibrinopeptide A (FPA) and B beta 15-42 fragment, indices of platelet release, thrombin generation and plasmin activity respectively, were measured in 32 high risk patients during a double blind study of a single dose of the anabolic steroid stanozolol (50 mg IM) in the prevention of DVT after major gastro-intestinal surgery. The prevalence of malignancy and the incidence of DVT (125I fibrinogen scan) were similar in the two treatment groups. On the first postoperative day, BTG, FPA and B beta 15-42 levels were increased in most patients. Plasma BTG levels were significantly increased on the first post-operative day in patients who developed a DVT (n = 14) compared to those patients who did not (n = 18). A significant increase in FPA levels was found in the DVT group, 7 days after surgery. On the morning before surgery, plasma B beta 15-42 levels were significantly increased in patients who developed a DVT. In patients undergoing surgery for early malignancy (n = 17), we observed a pre-operative increase in FPA levels when compared to patients without malignancy. At post-operative day 7, B beta 15-42 levels were significantly increased in patients who received stanozolol (n = 15), when compared to the placebo group, suggesting that intramuscular stanozolol increases fibrinolysis in vivo.
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PMID:Plasma beta-thromboglobulin, fibrinopeptide A and B beta 15-42 antigen in relation to postoperative DVT, malignancy and stanozolol treatment. 241 Sep 95

This study comprised 50 patients subjected to major abdominal surgery, of which 13 developed deep vein thrombosis (DVT) according to the 125I-fibrinogen test. Plasma was sampled preoperatively, for the specific analysis of tissue plasminogen activator (t-PA) before and during venous occlusion. The recently described fast t-PA inhibitor and plasmin alpha 2-antiplasmin complex (PAP) were also measured. The result of the laboratory analyses were correlated to the development of DVT. From the data obtained it is concluded that the evaluation of t-PA release during venous occlusion is a poor predictive factor for the occurrence of DVT after major abdominal surgery. The level of the t-PA inhibitor appears to be raised in these patients, but the values obtained in this material were not related to the development of postoperative DVT. Patients with elevated PAP levels, as shown previously, have a lesser tendency to develop postoperative DVT.
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PMID:Relationship between preoperative status of the fibrinolytic system and occurrence of deep vein thrombosis after major abdominal surgery. 241 Oct

An enzyme-linked immunosorbent assay (ELISA) is developed for the measurement of plasmin-alpha 2-antiplasmin complex in human plasma. Microtiter plates were coated with a mixture of two murine monoclonal antibodies directed against human alpha 2-antiplasmin and bound plasmin-alpha 2-antiplasmin complex was quantitated with a peroxidase-conjugated monoclonal antibody directed against human plasminogen. The lower limit of sensitivity of the assay was 0.01 nM of plasmin-alpha 2-antiplasmin complex in 100-fold diluted human plasma, allowing detection of 1 nM in undiluted plasma samples. After 100-fold dilution of the plasma samples, the assay was no longer influenced by the presence of the precursors plasminogen and alpha 2-antiplasmin. At a concentration of 2.0 nM of plasmin-alpha 2-antiplasmin complex in plasma, intra- and interassay variation coefficients were 4.2 and 5.5 percent respectively. In plasma samples of 25 control subjects the levels of plasmin-alpha 2-antiplasmin complex were below 1 nM. Extensive in vivo activation of the fibrinolytic system during thrombolytic therapy with streptokinase resulted in the generation of elevated levels of plasmin-alpha 2-antiplasmin complex up to 690 +/- 150 nM. No measurable levels of plasmin-alpha 2-antiplasmin complex were found in the plasma of 32 patients with acute deep vein thrombosis nor in the plasma of 11 patients with recurrent deep vein thrombosis. These findings indicate that plasmin-alpha 2-antiplasmin complex is generated during in vivo activation of the fibrinolytic system and that its assay may be useful to monitor thrombolytic therapy but not for the diagnosis of venous thrombosis.
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PMID:An enzyme-linked immunosorbent assay (ELISA) for the measurement of plasmin-alpha 2-antiplasmin complex in human plasma--application to the detection of in vivo activation of the fibrinolytic system. 243 84


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