Streptokinase Thrombolytics

Thrombolytics (aka fibrinolytics) are of clinical value in the early treatment of fibrin-clot-induced ischemia (e.g., >60% decrease in post-MI mortality if used within 3 h). The general and clinical i features of the primary thrombolytics, streptokinase, and alteplase are discussed. 

The client diagnosed with a massive pulmonary embolus is ordered the thrombolytic streptokinase. The nurse notes on the Medication Administration Record that the client is allergic to the -mycin medications, including streptomycin. Which action should the nurse implement ... 

Streptokinase has an initial plasma half-life (/ 2 of 18 min, and a P half-life of 83 min (73) it is well recognized that the thrombolytic efficacy of the enzyme decreases as the age of the thrombus increases thus, thrombolysis is significantly decreased when therapy is initiated more than three hours after an occlusion (74). 

Several clinical trials have been conducted with streptokinase adrninistered either intravenously or by direct infusion into a catheterized coronary artery. The results from 33 randomized trials conducted between 1959 and 1984 have been examined (75), and show a significant decrease in mortaUty rate (15.4%) in enzyme-treated patients vs matched controls (19.2%). These results correlate well with an ItaUan study encompassing 11,806 patients (76), in which the overall reduction in mortaUty was 19% in the streptokinase-treated group, ie, 1.5 million units adrninistered intravenously, compared with placebo-treated controls. The trial also shows that a delay in the initiation of treatment over six hours after the onset of symptoms nullifies any benefit from this type of thrombolytic therapy. Conversely, patients treated within one hour from the onset of symptoms had a remarkable decrease in mortaUty (47%). The benefits of streptokinase therapy, especially in the latter group of patients, was stiU evident in a one-year foUow-up (77). In addition to reducing mortahty rate, there was an improvement in left ventricular function and a reduction in the size of infarction. Thus early treatment with streptokinase is essential. 

The thrombolytic efficacy of streptokinase treatment may be compromised by the presence of antibodies to the enzyme in the patient s blood. 

Anistreplase has a considerably longer a half-life than streptokinase, ie, 90 min compared to 20 min (87,88). Moreover, it does not require prolonged infusion to achieve its thrombolytic effects. Anistreplase was found to be highly effective after a single intravenous dose of 30 units over a 5-min period compared to a 60-min infusion of 1.5 million units of streptokinase (89—94). In direct comparative studies, anistreplase was as effective as intracoronary (95,96) and intravenously (96—100) adrninistered streptokinase. In a randomized, double-blind, placebo-controUed study (AIMS trial) with 1004 patients given this modified enzyme, the 30-day mortaUty rate was 12.2% for patients receiving placebo, compared to 6.4% for patients who received 30 units of anistreplase intravenously within six hours of the onset of symptoms (101). 

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

One drawback of thrombolytic therapy is a high incidence of reocclusion. In a report using a canine model, inclusion of heparin [9005-49-6] (anticoagulant therapy) in the treatment prevented this side effect (158). The combination of aspirin [50-78-2] (antiplatelet therapy) and streptokinase (thrombolytic therapy) has also shown significant therapeutic advantages (78). Although additional work is needed to estabUsh the thrombolytic advantage of various combinations, preliminary results in this area indicate promise in terms of increased efficacy and reduced side effects. 

A patient enters the emergency department with an acute MI. Thrombolytic therapy is begun with streptokinase Discuss ongoing assessments that are important for the nurse to perform. 

Krumholz HM, Pasternak RC, Weinstein MC, et al. Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction. N Engl J Med 1992 327 7-13. 

Table 51-3. Comparison of some properties of streptokinase (SK) and tissue plasminogen activator (t-PA) with regard to their use as thrombolytic agentsJ...

Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial-Europe study group. N Engl J Med. 1996 335 145-150. 

Combination GP Ilb/IIIa and rt-PA Therapy for Acute Stroke The combination of antiplatelet and thrombolytic drugs has proven efficacy in the setting of myocardial ischemia where an additive effect is seen. In acute stroke thrombolysis with a very narrow time window and less than 50% optimal reperfusion rates,adjunctive therapy with antiplatelets may be a promising approach. However, MAST-I concluded that the group of patients receiving streptokinase plus aspirin had a marked increase in 10-day mortality. 

Streptokinase is not indicated for use in acute ischemic stroke treatment. Three large randomized controlled trials evaluating streptokinase were stopped early due to a high incidence of hemorrhage in the streptokinase-treated patients.14-16 At the present time, there is no indication for the use of streptokinase or thrombolytics other than alteplase in the acute treatment of ischemic stroke. 

Alteplase has proven effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event) are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min) results in a steady-state alteplase concentration of 3-4 mg l 1 during that period. However, the product is cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

Streptokinase is a widely employed thrombolytic agent. It is administered to treat a variety of thrombo-embolic disorders, including ... 

Streptokinase induces its thrombolytic effect by binding specifically and tightly to plasminogen. This induces a conformational change in the plasminogen molecule that renders it proteolytically active. In this way, the streptokinase-plasminogen complex catalyses the proteolytic conversion of plasminogen to active plasmin. 

Although staphylokinase shows no significant homology with streptokinase, it induces a thrombolytic effect by a somewhat similar mechanism it also forms a 1 1 stoichiometric complex with plasminogen. The proposed mechanism by which staphylokinase induces plasminogen activation... 

Banerjee, A., Chisti, Y., and Banerjee, U.C. 2004. Streptokinase - a clinically useful thrombolytic agent. Biotechnology Advances 22(4), 287-307. 

Human recombinant tPA and streptokinase are used as thrombolytic agents e.g. they are infused into the bloodstream as soon as possible after a heart attack. 

Although most of the enzyme-based drugs are inhibitors of enzymes, a number of enzyme preparations have also been developed as drugs for the treatment of a number of diseases. The development of enzymes as therapeutics has been made easier due to the advances in biotechnology. Most successful example of enzyme therapy includes various preparations of plasminogen activators (thrombolytic or fibrinolytic agents) such as a bacterial protein streptokinase and two plasminogen activators... 

Banerjee A, Chisti Y, Banerjee UC. Streptokinase -a clinically useful thrombolytic agent. Biotechnol Adv 2004 22 287-307. 

Concomitant use with thrombolytic therapy Clinical trials in HIT patients have provided only limited information on the combined use of lepirudin and thrombolytic agents. The following dosage regimen of lepirudin was used in 9 HIT patients in the studies who presented with TECs at baseline and were started on both lepirudin and thrombolytic therapy (alteplase, urokinase, or streptokinase). 

Intracranial bleeding Following concomitant thrombolytic therapy with alteplase (tPA) or streptokinase may be life-threatening. Carefully assess the risk of lepirudin administration vs its anticipated benefit in patients with increased risk of bleeding. In particular, this includes the following conditions ... 

Allergic reactions Approximately 53% of all allergic reactions or suspected allergic reactions occurred in patients who concomitantly received thrombolytic therapy (eg, streptokinase) for acute Ml or contrast media for coronary angiography (see Adverse Reactions). 

Drugs that may interact with lepirudin and increase the risk of bleeding include thrombolytics (eg, tPA, streptokinase) and coumarin derivatives (vitamin K antagonists). 

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

The major toxicity of all thrombolytic agents is hemorrhage. Streptokinase can cause allergic reactions with fever, rash and, although rarely, anaphylaxis. 

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