Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventional thrombolytic therapy with streptokinase (SK) at the standard dose (loading dose, 250,000 IU; maintenance dose, 100,000 IU/h) after recent surgery may provoke a tendency towards severe bleeding secondary to plasminaemia associated with clotting disorders. In contrast, ultrahigh-dose SK therapy regimen (loading dose, 4 million IU; maintenance dose, 1-2 million IU/h) can minimize the risk of bleeding. Since the circulating plasminogen (Plg) can immediately bind to SK to form the so-called SK-Plg activator complex, free plasminogen is no longer available for conversion to systemic plasmin. In a pilot study, greater than 30 patients presenting with acute respiratory distress syndrome (ARDS) received ultrahigh-dose SK therapy following recent surgery. Although the period between surgery and thrombolysis was 2.5 days on average, no major haemorrhages occurred. In addition, a surprisingly high survival of 50% was reported. Although the efficacy of the ultrahigh-dose SK regimen in ARDS has not been definitively confirmed, this regimen is well accepted for the treatment of severe pulmonary embolism after surgery. Another promising indication for the use of this therapy is catheter-induced thrombosis of the major central veins. Additional, albeit rare, situations in which this treatment can be used include intrabronchial administration of thrombolytic agents after blood aspiration or their selective intravenous use following severe venous thrombosis in high-risk patients. This paper demonstrates the feasibility of thrombolytic therapy in these indications and discusses the benefit/risk ratio of the different agents tested.
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PMID:[Fibrinolytic therapy in surgically treated intensive care patients]. 181 12

Tissue-type plasminogen activator (t-PA) is a serine protease that converts a zymogen plasminogen into an active serine protease, namely, plasmin. Plasmin is the proteolytic enzyme that degrades fibrin. In the absence of fibrin, e.g., in circulating plasma, t-PA activates plasminogen at a very slow rate. However, when fibrin is present, this activity is enhanced two to three orders of magnitude. As a consequence of these kinetic characteristics, plasmin is predominantly generated on the fibrin surface. This in turn results in a relative sparing of circulating fibrinogen and other plasma proteins to plasmin--mediated degradation. Following the demonstration of the potential of natural t-PA as a thrombolytic agent, an intensive effort was launched to enhance its production by recombinant DNA technology. The pharmacological action and the clinical efficacy of t-PA has been tested by several Authors in the treatment of acute myocardial infarction (AMI), and more recently, of pulmonary embolism, a condition for which this drug seems to be very promising: from this point of view this short article provides evidence that the various thrombolytic agents are of equal ability in mediating the rapid lysis of a coronary thrombus after i.v. administration when given appropriately and at the proper time; clinical experience provides little support for the contention of the superiority of t-PA over other thrombolytic agents, particularly for coronary thrombolysis. We are waiting for the results that will come from the GISSI-2 study, that is comparing streptokinase (SK) vs. t-PA in AMI's patients.
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PMID:[Tissue-type plasminogen activator]. 211 66

We describe two families with heterozygous plasminogen deficiency. In the first the patient was a 27 year-old female who suffered an acute episode of ischemic cerebrovascular disease affecting the left temporal lobe documented by arteriographic, gammagraphic and CAT studies. She had no family history of thrombotic conditions. In the other family the propositus was a 31 year-old man with spontaneous deep venous thrombosis in the left leg. His father was also symptomatic, with a history of recurrent thrombotic complications after predisposing factors, that included multiple venous thrombosis and a pulmonary embolism. Laboratory data showed normal hemostasis test results. Antigenic and functional levels of protein C, protein S and antithrombin III were within normal limits. The only abnormality found was decreased plasminogen activity in plasma; antigenic and functional levels were reduced to about half-normal levels. In both cases crossed immunoelectrophoresis revealed a normal migration pattern of plasminogen. Thus, we conclude that our patients were carriers of congenital hypoplasminogenemia or familial type I plasminogen deficiency, due to decreased synthesis. We also reported on fibrinolytic response to infusion of DDAVP, a synthetic analogue of the antidiuretic hormone. Fibrinolytic activity was normal in basal conditions as well as in response to DDAVP infusion.
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PMID:[Plasminogen deficiencies in 2 Spanish families. Response to the administration of DDAVP]. 236 94

Tissue-type plasminogen activator (t-PA), an important component of the fibrinolytic system, is now available as a biotechnologically manufactured recombinant protein for therapeutic use. It has proved highly effective in the clinical therapy of acute thromboembolic diseases such as myocardial infarction and pulmonary embolism. t-PA activates plasminogen to plasmin, which subsequently dissolves the fibrin network of a blood clot. This activation by t-PA occurs selectively on the clot surface, with negligible systemic side effects. The half-life of t-PA in vivo is in the order of minutes due to rapid hepatic elimination. t-PA is a glycoprotein with serine protease activity and consists of a polypeptide chain with 527 amino acids. Recently, intensive research efforts have been devoted to modification of the molecular structure of t-PA, with the objective of further increasing fibrin specificity and catalytic activity, or reducing the rate of elimination. As a result, considerable insights into structure-function relationships within the t-PA molecule have been gained, but as yet no clinically utilizable variant has been constructed which is in all respects superior to naturally occurring t-PA.
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PMID:Properties of molecular variants of tissue-type plasminogen activator. 250 92

Pulmonary embolism can produce severe cardiopulmonary dysfunction characterized by pulmonary artery hypertension, right ventricular failure, and hypoxemia. The search for the source of a pulmonary embolus, by exploration of the veins of the lower limbs and the inferior vena cava should be systematically carried out in all cases of pulmonary embolus which are not immediately life-threatening to the patient. The treatment of deep vein thrombosis associated with pulmonary embolism with thrombolytic agents has been proposed and utilized for approximately 20 years. Although superior results have been claimed with thrombolytic agents, the use of this type of treatment remains limited to massive or sub-massive pulmonary embolism. Fibrinolytic agents with high specificity for fibrin in the thrombi and little systemic activation of the fibrinolytic system have been developed and tested in preliminary clinical trials of patients with acute pulmonary embolism. The largest published experience available has been with recombinant tissue plasminogen activator (rtPA). The acylated streptokinase-plasminogen complex (APSAC) and pro-urokinase also gave promising results. All these agents were accompanied by unexpectedly high incidence of systemic activation of the fibrinolytic system and by hemorrhagic complications with frequencies similar to those that follows the use of first generation products (urokinase and streptokinase). Hence, their superior clinical efficacy must be clearly proven before they are substituted for a more widely available and less expensive drug, such as streptokinase.
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PMID:Pathogenesis and management of acute pulmonary embolism. 251 49

The ability of streptokinase and urokinase to lyse intravascular fibrin-based clots is firmly established. However, there is a lack of enthusiasm for these agents because of serious haemorrhagic complications and a lack of controlled randomized studies indicating their efficacy. Thrombolytic therapy is suitable in only 15 per cent of patients with acute deep venous thrombosis. It restores the venous circulation to normal in up to 95 per cent of these patients if therapy is instituted within 5 days of the onset of symptoms. These patients have significantly fewer symptoms on follow-up than patients treated with heparin although the ability of thrombolytic therapy to preserve venous valvular function and to prevent the post-phlebitic syndrome is now in question. Thrombolytic therapy is as effective as heparin in preventing pulmonary embolism and may be superior in its treatment. Pulmonary haemodynamics are rapidly improved, diffusion capacity is restored and, although the evidence is inconclusive, long-term pulmonary hypertension may be prevented. Although the mortality rate is not decreased, controlled studies show that thrombolytic therapy may be beneficial in massive pulmonary embolism with clinical shock. Thrombolytic therapy is indicated for acute arterial and acute bypass graft occlusion when the surgical alternative is associated with a higher morbidity and mortality. Partial thrombolysis is achieved in up to 90 per cent of cases and the need for further therapeutic intervention is eliminated in one-third of the patients treated. New thrombolytic agents with greater specificity and potentially greater efficacy and fewer complications are being developed. Tissue plasminogen activator has been successfully used. Prourokinase, fibrin-seeking urokinase and acetylated streptokinase-plasminogen complex may expand the role of thrombolytic therapy in surgical practice.
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PMID:The role of thrombolytic therapy in surgical practice. 265 13

Clinical experience with thrombolytics in non-coronary disorders is limited to the plasminogen activators streptokinase, urokinase and alteplase; therapeutic trials with anistreplase (APSAC) are almost, and with saruplase completely, limited to acute myocardial infarction. In terms of thrombus clearance, thrombolytic drugs are superior to heparin in patients with recent deep vein thrombosis in the pelvis or lower limbs. In aggregate, thrombi younger than 8 days are lysed in approximately 60% of patients treated with streptokinase, urokinase or alteplase. The results of studies assessing the subsequent development of the postphlebitic syndrome are conflicting, but most suggest that thrombolytic therapy can reduce symptoms of chronic venous insufficiency. Currently, the combination of systemic thrombolytic drugs followed by heparin is recommended for patients with acute major pulmonary embolism who are haemodynamically unstable. Streptokinase, urokinase and alteplase have all been shown to accelerate the lysis of pulmonary emboli and to decrease pulmonary vascular obstruction and pulmonary hypertension. Systemic venous or intrapulmonary infusions of alteplase offers the same benefit in terms of angiographic and haemodynamic improvement. A short infusion of 100 mg alteplase over 2 hours seems to be superior to a 24-hour infusion of urokinase. None of the thrombolytic trials in pulmonary embolism have been large enough to demonstrate a reduction in mortality. It is now generally accepted that, unless contraindicated, thrombolytic therapy is the front-line treatment for patients with massive pulmonary embolism and major haemodynamic disturbance. The local treatment of acute arterial occlusion in limb arteries results in rapid clearing of the artery in 67% of patients treated with streptokinase; the corresponding success rates for urokinase and alteplase are 81% and 88 to 94%, respectively. The main question appears to be the identification of patients in whom local thrombolysis is the treatment of choice, as opposed to established therapeutic modalities. Thrombolytic treatment following a major ischaemic stroke is hazardous, although clinical improvement has been noted in a minority of patients with recanalised cerebral arteries. The safety and efficacy of thrombolytic treatment remains unproven for this indication, and its use must be restricted to experimental protocols. Thrombolytic treatment in retinal artery or vein occlusion has, in practice, been abandoned.
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PMID:Use of thrombolytic drugs in non-coronary disorders. 268 38

Oral contraceptives (OCs) and surgery are both recognized risk factors for thromboembolism. Observation of a postoperative deep venous thrombosis and pulmonary embolism in a 21-year-old OC user prompted the authors to define the risk of OC use in surgical patients through a review of the literature. The patient had no other relevant risk factors except a moderate smoking habit. Surgery increases risk of thromboembolism because of the postoperative hypercoagulation state with declines in AT III, elevation of fibrinogen and products of degradation of fibrin, decline of plasminogen, and elevation of antiplasmin. The risks are greater in the immobile postsurgical phase and are increased as well by direct vascular lesions during surgery. Estimates of rates of deep venous thrombosis are very variable according to different authors because of the difficulties of diagnosis, heterogeneity of risk factors encountered, and variety of prophylactic methods employed. The most thrombogenic surgery is believed to be that on the legs; 1 literature review produced a range of estimates from 45-70% without prophylaxis and with 2% involving fatal pulmonary emboli. Another study estimated the risk of deep venous thrombosis at 2% for young subjects in good health undergoing minor surgery lasting less than 30 minutes and at 10-40% for subjects over 40 undergoing moderately serious general surgical procedures. No ideal method of prevention has been found that is well accepted by patients, nurses, and physicians. OC use entails multiple physiopathologic modifications including among others alterations of the vascular walls with endothelial proliferation and/or thickening of the media, increased blood viscosity, hyperaggregability of platelets, and increases in certain coagulation factors. Synthetic estrogens play the major role in modifications but progestins diminish venous tone and increase stasis. Large epidemiologic studies in the US and Great Britain found a significantly increased thromboembolic risk in OC users beginning in the 1st month of use and persisting until 3-4 weeks after termination of treatment. Most authors believe that OC use increases the postsurgical risk of thromboembolism by a factor of about 3. More selective choice of OC users, reduced estrogen doses, and better surveillance of users appear to have diminished the risk of thromboembolic disease with OC use. But unfortunately there are no sure predictors of thromboembolic disease. All authors recognize the reversibility of modifications caused by OCs on hemostasis by 4 weeks after termination. If therefore is recommended that OC use be interrupted 1 cycle before surgery.
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PMID:[Oral contraception and surgery]. 269 Oct 23

Between October 1982 and July 1984 systemic thrombolysis was carried out in 10 patients (5 males and 5 females aged 19 to 66 years) with massive pulmonary embolism (PE). Mean thrombolytic treatment duration was 77 hours. The main fibrinolytic agent used (9 cases) was streptokinase. Sequential treatment with streptokinase and urokinase was given to 2 patients and urokinase alone to one. 5 patients received porcine plasmin additionally, and one patient BRL 26921 (streptokinase-plasminogen complex) and human plasminogen. Pulmonary arterial pressures were recorded serially. Pulmonary angiograms were obtained before, occasionally during and after thrombolysis. Pulmonary arterial pressures (systolic: p less than 0.01, diastolic: p less than 0.05, mean: p less than 0.01, paired t-test, two tailed) and pulmonary angiograms (p less than 0.001, paired t-test, two tailed) all showed significant improvement. Thrombolytic treatment had to be discontinued in two patients due to side effects. Patients with the most recent PE showed the best response. Patients with recurrent PE and preexisting pulmonary hypertension showed no improvement. In PE without deep vein thrombosis (DVT), treatment duration of up to three days seems to be appropriate. In PE with concomitant DVT the treatment should be prolonged to achieve complete lysis of thrombi.
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PMID:[Fibrinolysis therapy in massive lung embolism. Experiences in 10 patients 1982-1984]. 293

A new abnormal plasminogen, Frankfurt I, has been identified in the plasma of a 42 year-old male patients who had recurring thromboses, thrombophlebitis and pulmonary embolism since his age of 29. Reduced functional and also slightly reduced antigen plasminogen concentrations were found in both the proposituts and his mother. Plasmin generation rates carried out by Streptokinase and Urokinase were also abnormal. The plasmin generated was very unstable in the absence of stabilizing ligands and/or substrates. Crossed immunoelectrophoresis of the purified Frankfurt I revealed a peak with normal size and shape, but displaced with respect to normal Glu-plasminogen toward the anode. Isoelectric focusing followed by zymography on an agarose-fibrin plate proved this observation but did not indicate a separation of the normal from the abnormal plasminogen molecular species, also, fewer bands were found in the abnormal plasminogen isozyme pattern. Kinetic studies of Frankfurt I Glu-plasminogen and plasmin showed that most of the functional abnormality is related to absence of active sites in half of the molecules.
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PMID:Congenital abnormal plasminogen, Frankfurt I, a cause for recurrent venous thrombosis. 296 86


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