Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Use of urokinase to treat heparin-associated thrombocytopenia and thrombosis in one patient is described, and various treatments proposed for this syndrome are discussed. A 56-year-old man received an intravenous bolus dose of heparin sodium at his local hospital and was transferred to another institution for treatment of suspected pulmonary embolism; he had received heparin two weeks earlier during coronary angiography. The patient's platelet count was reported to be normal before heparin administration. When embolism was confirmed, heparin was discontinued and streptokinase was given for 24 hours. Heparin infusion was then restarted at 1000 units/hr and continued for four days. Platelet count on admission to the second hospital was 47,000/cu mm; 12 hours later it was 19,000/cu mm, and it remained low despite platelet transfusions. Five days after admission, deep-vein thrombosis developed in the left leg. Heparin was discontinued and urokinase and warfarin were started. Urokinase was infused at 320,000 IU/hr for 12 hours and continued at dosages of 160,000-320,000 IU/hr for a total of 40 hours. The initial warfarin sodium dose was 15 mg, followed by a dosage of 10 mg/day. Symptoms of deep-vein thrombosis improved within 12 hours and platelet count increased after heparin was discontinued. If it is recognized early enough, heparin-associated thrombocytopenia can be reversed by discontinuation of heparin. Transfusions of platelets are of little benefit. Dipyridamole, cyclo-oxygenase inhibitors such as aspirin, and protamine sulfate may be useful. Long term anticoagulation with warfarin is recommended to prevent recurrent thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolytic therapy in heparin-associated thrombocytopenia with thrombosis. 348 69

Dipyridamole, an inhibitor of platelet aggregation, has been shown to have beneficial effects in disorders characterized by extravascular fibrin deposition. Mononuclear phagocytes are present in extravascular sites and are capable of expressing both plasminogen activator and procoagulant activities, which suggests these cells play a central role in extravascular fibrin turnover. We therefore sought to determine whether dipyridamole affects the expression of plasminogen activator and procoagulant activities by rabbit alveolar macrophages cultured in vitro. We found that dipyridamole (10 to 100 mumol/L) caused increases in both cell-associated and released plasminogen activator activity, which reached levels of 240% (P less than .05) and 543% (P less than .01) of controls, respectively. In contrast, dipyridamole decreased the cell-associated procoagulant activity of alveolar macrophages to as little as 21.3% of controls (P less than .01). Similar effects were seen in cells cotreated with lymphokines. The procoagulant activity expressed by these cells functioned as a tissue thromboplastin. The plasminogen activator of control and treated cells was a urokinase as determined by molecular weight characteristics (50 kilodaltons) and by antibody neutralization profiles using polyclonal antibodies against human urokinase and tissue plasminogen activator. These effects of dipyridamole could not be duplicated by structurally dissimilar agents sharing some of the pharmacological actions of dipyridamole; however, two pyrimidopyrimidine compounds structurally similar to dipyridamole effectively mimicked the effects on both procoagulant and plasminogen activator activities. We conclude that dipyridamole may have antithrombotic effects by directly modulating the role of mononuclear phagocytes in fibrin turnover. Thus, dipyridamole may be useful in situations where extravascular fibrin deposition is important to the pathogenesis of tissue injury and repair.
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PMID:Dipyridamole stimulates urokinase production and suppresses procoagulant activity of rabbit alveolar macrophages: a possible mechanism of antithrombotic action. 380 75

A 6-month-old female infant was seen with heart failure secondary to severe aortic and mitral regurgitation. As a neonate the infant had undergone an aortic valvotomy for congenital aortic stenosis. Subsequently the infant had aortic and mitral regurgitation with an infarcted papillary muscle. Double valve replacement was carried out with the St. Jude valve. The first approach was by the Manouguian procedure with extension of the aortotomy out between the left coronary cusp and the noncoronary cusp. The posterior mitral apparatus was resected, and a 19-mm St. Jude aortic valve was sewn into the mitral position. Because the enlarged aortic valve annulus was still inadequate to accommodate a 19-mm St. Jude valve, a Konno procedure was carried out to enlarge the aortic ring anteriorly. Atrial, septal, and aortic repair and right ventricular outflow tract reconstruction were carried out with bovine pericardium. Bypass was carried out with standard techniques of hypothermia, aortic cross-clamping, and cardioplegia. Postoperative anticoagulation therapy was initially with aspirin and dipyridamole (Persantine); however, clotting of the mitral prosthesis necessitated treatment with urokinase and heparin, which completely resolved the clot. Sodium warfarin (Coumadin) therapy was then begun. One year postoperatively, the child is developing normally.
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PMID:Combined techniques for double valve replacement in the infant. 388 67