Tissue plasminogen activator infusion

A platelet transfusion Heparin infusion Thrombin infusion Fibrinogen infusion Tissue plasminogen activator Infusion... 

Bamgbola OF, del Rio M, Kaskel FJ, Flynn JT Recombinant tissue plasminogen activator infusion for hemodialysis catheter clearance. Pediatr Nephrol 2005 20 989-993. 

In the initial study described by Gold et al. (1984), recombinant t-PA was characterized for its ability to lyse 2-hour-old thrombi. Tissue plasminogen activator was infused at doses of 4.3, 10, and 25 (ig/kg/min, i.v, and resulted in reperfusion times of 40, 31, and 13 minutes, respectively. Thus, in this model of canine coronary thrombosis, t-PA exhibited dose-dependent coronary thrombolysis. Furthermore, it is possible to study the effect of different doses of t-PA on parameters of systemic fibrinolytic activation, such as fibrinogen, plasminogen, and a2-antiplasmin, as well as to assess myocardial infarct size. For example, Kopia et al. (1988) demonstrated that SK elicited dose-dependent thrombolysis in this model. 

The Cervene Stroke Study Investigation Group conducted a phase III study to assess the efficacy and safety of nalmefene (Cervene) in patients with acute ischemic strokes and also the safety of combined recombinant tissue plasminogen activator and nalmefene in a subset of patients (4). It was a randomized, placebo-controlled, double-blind study of a 24-hour infusion of nalmefene on 368 patients who received 60 mg nalmefene administered as 10 mg bolus over 15 minutes and then a 50 mg infusion over 24 hours or placebo. Even though nalmefene appeared safe and well tolerated, the study failed to find any benefit in stroke patients treated with nalmefene within six hours. 

Treatment requires a clot buster to remove the fibrin clot. Because plasminogen circulates in the blood in relatively large amounts, a common procedure is to give intravenous tissue plasminogen activator (tPA) to speed its conversion to plasmin (Fig. 11.10). Thus, intravenous tPA is the best therapy for acute symptoms of clot development. Because the half-life of infused tPA in blood plasma is only 4-5 min, it should be continuously infused for about an hour to dissolve enough clot to limit a potential ischemia. Recombinant human tPA is preferred to animal tPA because it is the natural protein and can be safely injected... 

Alteplase, reteplase Recombinant human protein 2-10 min Active tissue plasminogen activator, (t-PA) converts plasminogen to plasmin intravenous infusion (alteplase) or bolus doses (reteplase) required. Most expensive. Reteplase is somewhat longer-acting than alteplase... 

Tissue plasminogen activator tPA alteplase (Activase) 59.04 Plasma volume (0.05 Lkg- ) 0.083 (initial) IV bolus injection followed by IV infusion (1.0 in both) Thrombolytic agent used in acute myocardial infarction, acute ischemic stroke and pulmonary embolism... 

The issue of catheter clearance was discussed at a National Association of Vascular Access Networks (NAVAN) consensus conference in 2000 (Haire and Herbst 2000). The results of the conference can be summarized as (1) the inability to withdraw and/or infuse are the most frequent signs of catheter occlusion (2) treatment depends on etiology of obstruction (3) tissue plasminogen activator (t-PA) is considered the drug of choice for thrombotic occlusions (Table 6.1) and (4) future investigations for t-PA include thrombotic prophylaxis, adjunctive use with antibiotics, and infusions for venous thrombosis and embolism. Ponec et al. (2001) performed a prospective randomized trial comparing t-PA and placebo for the treatment of occluded central venous cath-... 

Currently, in both arterial and venous occlusion, newer products such as alteplase which is recombinant human tissue-type plasminogen activator where 10 mg is given as an intitial bolus and a further 90 mg infused over 2 hours are offering alternative regimens. Although costly they have apparent benefit in stroke and acute coronary syndromes. 

Alteplase was the first commercially available recombinant tissue-type plasminogen activator (rt-PA) (25), It has a plasma half-life of less than five minutes and is metabolized by the liver, This agent was initially hailed as fibrin-specific unlike its precursors (urokinase and streptokinase). It was thought that this would result in a better safety profile, but this has not been born out in either the coronary or the peripheral experience, where actually there may be a higher bleeding risk as infusion time increases. Alteplase is currently indicated for use in the treatment of myocardial infarction, acute ischemic stroke, and pulmonary embolism. 

Fong KL, Crysler CS, Mico BA, Boyle KE, Kopia GA, Kopaciewicz L, Lynn RE. Dose-dependent pharmacokinetics of recombinant tissue-type plasminogen activator in anesthetized dogs following intravenous infusion. Drug Metab Dis 1988 16 201-6. 

Gold HK, Leinbach RC, Garabedian HD et al. (1986) Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator prevention by a maintenance infusion. Circulation 73 347-352 Goldberg RK, Levine S, Fenster PE (1985) Management of patients after thrombolytic therapy for acute myocardial infarction. Clin Cardiol 8 455 159 Kopia GA, Kopaciewicz LJ, Ruffolo RR (1988) Coronary thrombolysis with intravenous streptokinase in the anesthetized dog a dose-response study. J Pharmacol Exp Ther 244 956-962... 

Smalling RW, Schumacher R, Morris D, et al. Improved infarct-related arterial patency after high dose, weight-adjusted, rapid infusion of tissue-type plasminogen activator in myocardial infarction results of a multicenter randomized trial of two dosage regimens. J Am Coll... 

From 1995 through 2002, we participated in four international randomized studies and one collaborative study with the University of Vermont in which pharmacological thrombolysis was employed with alteplase [tissue-type plasminogen activator (t-PA)] or tenecteplase [TNK-t-PA (TNK)]. In this chapter we summarize our experience with the cohorts of patients in all of these studies who were studied in the United Arab Emirates (UAE). The first of the studies was the Continuous Infusion versus Double Bolus of Alteplase (COBALT) study. The other three were Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT I, II, III) studies and a substudy in ASSENT II with the University of Vermont (4-8). The last study, a collaborative one with the University of Vermont, was the Enhanced Rapidity of RECanah-zation with Tenecteplase compared with Alteplase (ERRECTA) study, results of which have not yet been published. All of the patients participating in ERRECTA were patients in the UAE. 

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