Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the case of a man bedridden by deep venous thrombosis who was given intraclot instillations of recombinant tissue plasminogen activator with remarkable improvement. Although such aggressive treatment may be justified in severe cases, the role for thrombolytic agents for less symptomatic deep venous thrombosis is undefined. We discuss the question of when thrombolytic therapy should be considered. However, proper clinical trials are needed before firm recommendations can be made.
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PMID:Thrombolytic therapy for deep venous thrombosis? 1059 39

The antithrombotic activity of dermatan sulfate from avian crown with the mean molecular weight of 38000 was compared to those from bovine intestine with the mean molecular weight of 16000 in vivo and in vitro. In an in vitro test, bovine intestine dermatan sulfate exhibited stronger effects on stimulation of heparin cofactor II and activation of Glu-plasminogen by tissue plasminogen activator. In vivo, avian crown dermatan sulfate more effectively prevented the development of thrombus in a rat deep vein thrombosis model. The measurement of plasma levels of these two kinds of dermatan sulfate revealed that avian crown dermatan sulfate circulated in higher concentration and longer duration than bovine intestine dermatan sulfate after intravenous administration to rats.
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PMID:Antithrombotic activity of avian crown dermatan sulfate. 1063 69

A reduction in fibrinolysis has been described in association with thrombosis in the primary antiphospholipid syndrome (PAPS). In this study, we measured anti-tissue-type plasminogen activator (t-PA) antibodies and anti-fibrin-bound t-PA antibodies as possible causes of hypofibrinolysis in 39 patients with PAPS. We also evaluated the differences in anti t-PA antibodies between patients without previous thrombosis (20 patients) and patients with previous episodes of thrombosis (19 patients: deep vein thrombosis in nine, ischaemic stroke in six, arterial leg thrombosis in one, hepatic vein thrombosis in one, thrombophlebitis in one and cerebral venous thrombosis in one). Anti-t-PA antibodies were measured by an enzyme-linked immunosorbent assay (ELISA), and anti-t-PA fibrin-bound antibodies were measured by a solid-phase fibrin immunoassay (SOFIA) in 39 patients with PAPS and in 39 controls matched for gender and age. High levels of IgG anti-t-PA were found in three out of 39 patients with PAPS, and all three patients had a history of thrombosis; four other patients, one of whom had a history of thrombotic events, had high titres of antibodies directed against fibrin-bound t-PA. In addition, patients with ischaemic stroke had significantly higher levels of IgG anti-t-PA than patients without thrombosis (P = 0.029). In conclusion, our data showed that, in patients with PAPS, the highest levels of anti-t-PA antibodies were present in subjects with previous thrombotic events. The discrepancy in the results obtained with two methods of detection of anti-t-PA antibodies, ELISA and SOFIA, indicates a different interaction of the antibodies with the t-PA molecules, which are directly bound to polystyrene plates in ELISA and bound to fibrin as a bridging molecule in SOFIA.
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PMID:Antibodies to tissue-type plasminogen activator in plasma from patients with primary antiphospholipid syndrome. 1079 98

The goals of treatment of acute iliofemoral DVT should be prevention of fatal PE, reduction of pain and swelling of the involved leg, trying to stop the development of phlegmasia cerulea dolens and venous gangrene, prevention of disabling PTS by early removal of the blood clot, avoiding proximal venous obstruction, preserving normal, functioning valves in the leg veins, and preventing reflux. The authors recommend an aggressive approach with rapid removal of the occluding thrombus in the leg veins extending up into the iliac veins in active patients with a short history of symptomatic DVT, usually less than 7 days. This approach is not justified in chronically ill, bedridden, high-risk, or aged patients, or those with serious intercurrent disease or limited life expectancy. In these patients, such interventions can only be indicated for limb salvage in phlegmasia cerulea dolens when conservative treatment does not prevent the development of an acute compartment syndrome with venous gangrene. The preferred means of accomplishing early and quick removal of the thrombus is CDITT. Most of the authors' positive experience with thrombolysis is based on the use of urokinase. The Food and Drug Administration (FDA) has put this drug on temporary hold for almost 1 year. The alternative drugs (e.g., tissue plasminogen activator [tPA]) have not been tested for CDITT of DVT, and tPA is not FDA-approved for this indication. When there are contraindications or failure of thrombolysis, TE with a temporary AVF is a valid alternative.
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PMID:Indications for surgical treatment of iliofemoral vein thrombosis. 1080 68

Paradoxical embolism through a patent foramen ovale (PFO) can involve multiple organs simultaneously. The most commonly involved sites are the cerebrum and the extremities. Paradoxical embolism to coronary arteries or upper extremities is relatively uncommon. We report a case of acute pulmonary embolism and paradoxical embolism through a patent foramen ovale involving the left upper extremity, brain, and coronary artery. Early diagnosis in the emergency department was made by a trans-esophageal echocardiogram, and the patient was successfully treated with intravenous t-PA and heparin. Patients with acute pulmonary embolism or deep venous thrombosis who also develop signs of systemic embolism should be evaluated for a patent foramen ovale.
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PMID:Paradoxical embolism-report of a case involving four organ systems. 1180 70

Every patient with acute stroke who presents to a medical center that has appropriate resources should undergo evaluation for intravenous tPA therapy. Such therapy should not be given unless the patient meets strict eligibility criteria based on clinical, radiographic, and laboratory data. Intra-arterial thrombolysis may be a promising alternative to intravenous tPA therapy, but it should still be regarded as experimental. Daily aspirin therapy should be initiated immediately in most patients who do not receive intravenous tPA therapy and after 24 hours in most patients who receive this treatment. Measures should be taken to prevent medical complications, such as aspiration pneumonia, deep vein thrombosis, contractures, and pressure sores. Early initiation of rehabilitation can maximize stroke recovery. Whenever feasible, institutions should have stroke teams or units to streamline care and provide expertise for patients with acute stroke.
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PMID:Management of acute ischemic stroke. What is the role of tPA and antithrombotic agents? 1086 69

Patients in intensive care may be at high risk of in vivo platelet activation because comorbid conditions, such as infections, septicemia, shock, disseminated intravascular coagulation, and cancer represent procoagulant states. Hyperreactivity of platelets with or without a decline of cell count may result in thromboembolic complications potentially associated with the phenomenon of heparin-induced thrombocytopenia. We analyzed the data of 10 patients highly suspected of having heparin-induced thrombocytopenia during their intensive care treatment of 29 plus or minus 22 days. In seven patients, thrombocytopenia coincided with thromboembolic complications. Six patients had additionally undergone fibrinolytic therapy before starting activated partial thromboplastin time-adapted alternative anticoagulation with r-hirudin. In three patients, the platelet count decreased without a clinical manifestation, of heparin-induced thrombocytopenia. R-Hirudin treatment monitored by activated partial thromboplastin time and prothrombin time (PT) was effective and safe. The target value for activated partial thromboplastin time was a twofold prolongation. In four of five patients with deep venous thrombosis, a partial recanalization of the lower extremity could be achieved. Three patients with pulmonary embolism associated with deep venous thrombosis in two cases and in one additional case with an acute myocardial infarction did clinically profit from fibrinolysis with recombinant tissue plasminogen activator (rtPA) and r-hirudin treatment. Two lethal events probably caused by the underlying multimorbidity could not be prevented. No recurrence of thrombosis occurred, and there were no severe bleeding complications attributed to r-hirudin treatment. Platelet counts were significantly reduced on day 9.4 plus or minus 6.4 of heparin administration in all cases (>50% decrease related to the initial values) from 224,000 plus or minus 126,000/microL to 96,000 plus or minus 61,000/microL, and increased during rhirudin treatment to mean values of 224,000 plus or minus 126,000/microL. The heparin-induced platelet activation assay (HIPAA) assay was positive in 8/10 cases, whereas the PF4 enzyme-linked immunosorbent assay showed a positive result in four of eight analyzed cases. In four cases, the assays were concordantly positive. The PF4 enzyme-linked immunosorbent assay was not performed in two cases.
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PMID:Heparin-induced thrombocytopenia: a critical risk/benefit analysis of patients in intensive care treated with R-hirudin. 1089 75

Patients with acute ischemic stroke should be immediately transported to the nearest hospital for rapid evaluation and treatment. Intravenous t-PA within 3 hours of symptom onset is the recommended treatment for patients who meet the National Institute of Neurological Disorders and Stroke (NINDS) study eligibility criteria. Patients should be informed of the risk of symptomatic cerebral hemorrhage, and strict adherence to the NINDS study protocol is strongly recommended to optimize the risk-benefit ratio. Ischemic stroke patients who are not eligible for t-PA therapy should usually be started on aspirin. Intravenous heparin is not recommended as a standard treatment but may be considered for specific patient subgroups. Low-dose subcutaneous heparin is recommended for prophylaxis of deep vein thrombosis in immobilized patients. Management of stroke patients by a designated stroke team is recommended to facilitate prompt diagnosis and treatment and early initiation of rehabilitation therapy. We also recommend that physicians who manage patients with acute stroke maintain contact with local or regional stroke centers to facilitate referral of appropriate patients for intensive care or specialized diagnostic tests or therapies.
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PMID:Acute Ischemic Stroke. 1109 99

The strong fibrin affinity of recombinant tissue plasminogen activator (rt-PA) theoretically obviates continuous infusion or replacement of t-PA after direct intrathrombic injection. This hypothesis led the authors to evaluate single daily catheter-directed injection of rt-PA as a thrombolytic treatment for acute deep vein thrombosis of the lower extremity. Once-daily injection of rt-PA was performed in large thrombosed veins (popliteal or larger) with use of pulse-spray catheters and in small thrombosed veins in patients' calves with use of 3-4-F coaxial catheters. Patients received only full systemic anticoagulation on his/her patient care unit. This dosing regimen has been tested in 10 patients (12 legs) with a maximum dose of 50 mg per leg per day. Extensive thrombolysis was achieved in nine patients and partial thrombolysis was achieved in one patient, at an average total dose of 106 mg of rt-PA per leg. Minor bleeding was seen in three patients and no transfusions were needed. Our technique and the rationale for this pilot study is the focus of this article.
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PMID:Daily catheter-directed single dosing of t-PA in treatment of acute deep venous thrombosis of the lower extremity. 1126 90

The fibrinolytic system plays an important role in the physiological maintenance of blood flow and the dissolution of thrombi. Administration of fibrinolytic agents in indications such as myocardial infarction, pulmonary embolism, deep vein thrombosis or stroke, therefore, offers a rational means to dissolve pathological thrombi and restore vascular patency. The functional domains of the physiological tissue plasminogen activator (t-PA) provide fibrin specificity and serine protease activity for plasminogen cleavage and binding to liver receptors which gives the molecule a short half-life. In order to combat acute thromboembolic events such as myocardial infarction, the structure of the natural t-PA molecule was genetically modified to prolong its half-life, to increase its fibrin-specificity and to improve its resistance to plasminogen activator inhibitor. These features of TNK-t-PA allow bolus administration in emergency situations, early reperfusion of the blood vessel and a low rate of bleeding complications, thus improving the overall benefit to patients.
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PMID:Improving natural principles with genetic engineering: TNK-tissue plasminogen activator. 1145 85


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