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)

Fifty-six patients scheduled for total hip alloplasty were screened for deep venous thrombosis by means of 99mTc-plasmin scintimetry, 99mTc-plasmin scintigraphy and contact thermography. Investigations were performed on the seventh postoperative day, and a total of 112 legs were examined. Bilateral ascending phlebography was used as reference procedure, and the criteria for deep venous thrombosis were intraluminal filling defects at phlebography. Six patients developed unilateral deep venous thrombosis. All three screening procedures revealed many false positive and several false negative results. The nosographic sensitivity/specificity was 33%/75% for scintimetry, 50%/91% for scintigraphy and 33%/87% for contact thermography, respectively. It is concluded that all three tests are of no value as screening methods for deep venous thrombosis following major elective hip surgery.
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PMID:Contact thermography, 99mTc-plasmin scintimetry and 99mTc-plasmin scintigraphy as screening methods for deep venous thrombosis following major hip surgery. 296 1

In an open controlled study, 248 consecutive patients (age more than 40 yrs) admitted for major abdominal surgery were randomized to one of three prophylactic antithrombotic treatments. Eighty-five patients received subcutaneous heparin, 74 patients had graduated compression stockings to the knee (TED stockings), and 89 patients had both subcutaneous heparin and stockings. Treatment began on the evening before operation and continued to complete mobilization, or for not less than five days postoperatively. On the fourth or fifth postoperative day, the patients underwent a 99mTc-plasmin test of the lower limbs as a test for deep vein thrombosis. There were 29.7% positive tests in the stocking group, 29.4% in the group with heparin prophylaxis, and 25.8% in the combined group. Differences between treatments were not statistically significant.
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PMID:Venous thrombosis after abdominal surgery. A comparison between subcutaneous heparin and antithrombotic stockings, or both. 297 90

The influence of circulatory changes, which are secondary to deep venous thrombosis (DVT) in the leg, on result of radionuclide tests was studied in eight patients. Strain gauge plethysmography, a radionuclide blood-pool test and phlebography were performed both in the acute phase and during recovery up to 6 months after the initial admission. Morphological and functional changes were correlated with results from repeatedly performed 99Tcm-plasmin tests, a test currently used for diagnosis of DVT. In the acute phase, the thrombotic leg showed an increase in pooled blood and, in the case of proximal thrombosis, also impaired venous outflow. During the 6-month follow-up complete recanalization was observed in three patients and partial recanalization in five. The circulatory changes were found to recover progressively and earlier than the morphological changes. The 99Tcm-plasmin test was pathological at admission in all patients. It was normalized in parallel with plethysmography and blood-pool test results, at a time when morphological recovery was still incomplete. These findings confirm that a positive 99Tcm-plasmin test reflects haemodynamic changes which are secondary to the DVT rather than a specific binding of the radiopharmaceutical to the thrombus. The 99Tcm-plasmin test was normalized from 1 to more than 26 weeks after an acute DVT. This finding is of practical importance when using radionuclide tests for evaluation of acute recurrent DVT.
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PMID:Follow-up of circulatory changes secondary to deep venous thrombosis with special regards to radionuclide tests. 300 79

A 99mTc-plasmin test and phlebography were performed on 45 consecutive unselected patients with suspected deep vein thrombosis of the leg. Phlebography showed thrombosis in 15 cases. In fourteen of these patients there was a positive result in the plasmin test. Eleven other patients had a positive plasmin test result as well. The most common causes for a false-positive result in the plasmin test in the diagnosis of deep vein thrombosis were acute inflammatory disease and disturbance in venous flow without fresh thrombosis. The sensitivity of the plasmin test in the diagnosis of deep vein thrombosis was 93% and the specificity was 63%. It is concluded that the plasmin test can be used for the screening of deep vein thrombosis.
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PMID:99mTc-plasmin test in deep vein thrombosis of the leg. 315 39

We have studied the effects of urokinase (UK) on concentration changes of alpha 2 antiplasmin (alpha 2 AP) and on fibrino(geno)lysis. Medium dose (480,000 u) or large dose (960,000 u) of UK was given to each of seven normal volunteers by intravenous drip infusion within six hours, and then blood and urine analyses were carried out. Total alpha 2 AP, which includes free alpha 2 AP and alpha 2 AP-plasmin complex, decreased to about 50% of the original value with large dose of UK. alpha 2 AP-plasmin complex appeared in the plasma one hr after UK infusion and increased up to 50% of total alpha 2 AP at the end of UK infusion. B beta peptides, which are liberated from fibrin(ogen) at the very early stage of fibrino(geno)lysis, increased significantly with UK infusion, and was 65 times as much as the normal range at the end of UK infusion. Urinary B beta peptides increased as well as plasma B beta peptides. On the other hand, fibrin(ogen) degradation products (FDP) measured with enzyme immunoassay (EIA) increased only slightly, and moreover, urinary FDP was not detectable at any time. Plasma fibrinogen levels did not decrease and changed within the normal range in both groups. We then gave 960,000 u of UK to four patients with deep vein thrombosis and blood analyses were carried out as with normal volunteers. The most significant observation different from that of normal volunteers was shown in FDP levels. Serum FDP levels of four patients increased significantly in comparison with normal volunteers. Urinary FDP increased as significantly as plasma FDP. In conclusion, the infusion of 960,000 u of UK caused only very early stage of fibrinogenolysis without advanced fibrinogenolysis in normal volunteers, but in thrombotic patients, advanced fibrinolysis was observed.
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PMID:Fibrinogenolysis and fibrinolysis in normal volunteers and patients with thrombosis after infusion of urokinase. 316 Dec 12

Since the introduction of thrombolytic treatment based on the activation of plasminogen (PLG) by streptokinase (SK) and urokinase (UK) the search for new and improved methods has been continuing. The pivotal issue is how to achieve clot-specific fibrinolysis without producing systemic fibrinogenolysis. One out of various approaches to enhance lysis rates has been the use of PLG either alone or in combination with UK or SK in the light of the fact that fibrinolytic treatment, particularly using SK, is associated with a consumption of PLG, and that thrombi contain relatively small amounts of native PLG, however, are capable of incorporating added PLG in vitro. PLG-concentrates from various manufactures have been administered intravenously for treatment of deep venous thrombosis, mainly in combination with SK, and of pulmonary embolism in combination with UK. Local intracoronary and intraarterial administration in combination with UK has been reported in patients with myocardial infarction, and peripheral arterial occlusions, respectively. Lysis rates obtained in these studies were in most cases superior to results obtained with SK or UK alone, without increasing the incidence of bleeding complications. In addition, excellent results in larger group of patients with cerebral thrombosis were obtained with PLG alone. The encouraging results of these studies may be explained by the fact that all of the preparations used contained partially activated forms of PLG (commonly designated lys-PLG) to a greater or lesser extent. Lys-PLG has a higher affinity for fibrin than the native glu-PLG and is activated by UK or SK by a manyfold faster. These properties allow for a rapid formation of plasmin which--bound to fibrin--is also protected from the attack of neutralizing antiplasmin. The design and results of previous studies with lys-PLG concentrates will be reviewed and approaches to further improve fibrinolytic regimens with lys-PLG-concentrates discussed.
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PMID:Review of studies with plasminogen concentrates and proposals for further therapeutic strategies with plasminogen concentrates. 328 Apr 22

In 1933 Streptokinase (SK) was isolated from bacterial strains of haemolytic Streptococci. Since then it has become the widest spread drug for fibrinolysis. SK, a protein, consists of 415 aminoacids and has a molecular weight of 47,000u. Together with the plasminogen (PLG) of the blood it forms activator complexes, which then convert other PLG molecules of the blood to plasmin. Plasmin attacks and dissolves fibrin deposits. As a substance produced by bacteria SK stimulates antibody formation in the body, the titer will increase during therapy, and SK lysis should be terminated after 6 days of treatment. Usually SK is administered intravascularly to treat a wide range of diseases, associated with pathological activation of hemostasis, like deep vein thrombosis, pulmonary embolism, myocardial infarction etc.. Contraindications can be traced back to the effects of SK on coagulation and the immune system. Bleeding is the most common side effect, but also a few anaphylactic reactions, caused by massive antigen-antibody precipitation have been observed. The rate of lethality of the treatment was established at 0.7% of the cases. To reduce the incidence of side effects modifications of the drug have been proposed, such as activator complex, light B chain SK, and acylated activator therapy. Compared with Urokinase, SK shows a higher rate of side effects, especially in the field of the immune system. Therapy with Urokinase can be controlled more easily. Nevertheless because of considerable price differences and logistics, SK is preferred in Europe and the USA. If strict guidelines in therapeutic use are followed, the rate of side effects of the drug can be curtailed and will be comparable to those of Urokinase.
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PMID:Review and current status of thrombolytic therapy with streptokinase. 354 44

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

In a prospective, controlled clinical study prevention of postoperative deep venous thrombosis by low-dose heparin (Heparin Leo 5 000 I.U. subcutaneously twice daily) was compared with graded compression stockings (TED stockings, Kendall Co.). One hundred and twelve patients, admitted during a period of one year for elective major surgery, were allocated to one of the two treatment groups. In order to detect deep venous thrombosis the 99mTc-plasmin test was performed before the operative procedure and again 5 days later. Ninety-seven patients completed the study (45 patients in the heparin group and 52 patients in the stocking group). Venous thromboembolism was detected in 4 patients (8.9%) in the heparin group and in 3 patients (5.8%) in the stocking group (p greater than 0.05). In 6 patients the plasmin test was positive and one patient in the heparin group died following pulmonary embolism. It is concluded that graded compression stockings can be used as an alternative to low-dose heparin for prophylaxis against deep venous thrombosis in elective general surgery.
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PMID:Prevention of postoperative deep venous thrombosis. Low-dose heparin versus graded pressure stockings. 389 94

The aim of these studies was to investigate different regimens of thrombolytic therapy and oral anticoagulation, and to evaluate the effects of streptokinase (SK), heparin and warfarin in the treatment of deep vein thrombosis (DVT). Low-dose SK, although controlled according to the fibrinogen levels, did not provide improved thrombolysis compared to conventional high-dose SK, and more postthrombotic changes were registered after an average of 3 years. Furthermore, serious hemorrhagic side-effects occurred, which makes this regimen inexpedient. Various regimens of local venous infusion of SK were tried, and with a dose of 4,000 IU/h for 72 h in combination with heparin a thrombolytic effect was achieved, albeit not greater than usually observed with conventional SK. Systemic hypofibrinogenemia and hemorrhage were not avoided. A hitherto not described side-effect with bullous dermatitis was reported. Venographic severity of calf vein thrombosis displayed a statistically significant correlation to long-term hemodynamic changes, as assessed with foot volumetry, after an average of 5 years. This correlation was stronger for the size of the thrombus after initial treatment than for the size at diagnosis. Thus it seems important to treat calf vein thrombosis with heparin in order to limit the extent of the thrombus, thereby reducing long-term sequelae. During heparin treatment, an average reduction of the thrombi of 17% was observed. This reduction was significantly correlated to a short duration of symptoms but not to parameters of heparin therapy or fibrinolytic components. However, patients with substantial thrombolysis had high plasmin-alpha 2-antiplasmin (PAP) levels, and those with high tissue plasminogen activator (t-PA) inhibitor levels and remarkably also those with high t-PA antigen levels had no lysis. The concentration of t-PA antigen showed a significant increase during heparin infusion, whereas that of PAP and t-PA inhibitor was not influenced. By applying more intensive initial oral anticoagulation, stable therapeutic prothrombin time (PT)-levels were achieved one day earlier and the duration of heparin infusion could be equally reduced compared to the conventional regimen (4.4-5 days vs 5.4-6 days). The activity of coagulation factors II, VII, IX and X had dropped to the same level with both regimens the day heparin was discontinued, observed. The effectiveness of oral anticoagulation after DVT was studied in 596 patients treated for a total of 4450 months.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Studies on the medical treatment of deep vein thrombosis. 391 82


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