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PubMed1986

Streptokinase in the treatment of subclavian vein thrombosis.

During the past 2 years, streptokinase has been used to treat subclavian or axillary vein thrombosis in seven patients of whom two were considered "effort" thromboses and five resulted from use of a central venous catheter. All patients had venography performed before treatment to document the thrombosis, and venography was repeated after streptokinase therapy to determine the status of clot dissolution. Streptokinase was given either systemically or in a lowered dose locally, with low-dose therapy chosen whenever a catheter could be threaded up to the clot through an antecubital vein. Although all seven patients had resolution of their clinical symptoms, only one had complete dissolution of the thrombus. The failure of streptokinase to completely dissolve the thrombus suggests that, although apparent clinical improvement can be achieved after streptokinase infusion, treatment of the underlying cause, whenever possible, may be necessary if complete resolution of the thrombus is to occur.

Adult↗

PubMed1986

Streptokinase treatment of cats with experimentally induced aortic thrombosis.

An investigation was initiated to determine the dosage of streptokinase (given IV) that would consistently produce systemic fibrinolysis, as determined by laboratory evaluation, and to determine the relative safety of this drug in the cat. Results indicated that a loading dose of 90,000 IU of streptokinase (given by continuous infusion over 20 to 30 minutes) and a maintenance dosage (IV) of 45,000 IU of streptokinase/hr predictably produced systemic fibrinolysis in the cat. There were no detectable adverse affects seen on physical examination, necropsy, or histopathologic examination. Using the foregoing dosage regimen, investigation was begun to evaluate the use of streptokinase for treatment of feline thromboembolism. Aortic thrombosis was created experimentally in 15 cats. There was no clearly predictable improvement in nonspecific venous angiograms or thermal circulatory indices for the cats given streptokinase, compared with the values for the control cats. After a total of 180 minutes of treatment, the mean weight of remaining clot removed at necropsy from the aortic trifurcation was 7.3 mg in the streptokinase-treated cats, compared with 13.4 mg in the control cats.

Angiography↗

PubMed1971

Comparison of the effects of streptokinase and heparin on the early rate of resolution of major pulmonary embolism.

The extent of early resolution of major pulmonary embolism observed in 10 patients after 24 hours of treatment with heparin was compared with that seen in 17 patients after 24 hours of treatment with streptokinase. The patients in the streptokinase group also received a loading dose of heparin and were treated with heparin by continuous infusion when their thrombin time returned to normal levels. All had pulmonary hypertension. Pulmonary embolism was classified as acute in the 10 patients in the heparin group. Seven of these patients showed no angiographic change, two showed slight improvement and one showed angiographic deterioration. There was a moderate and statistically insignificant fall in mean pulmonary arterial pressure and total pulmonary resistance. Fourteen of the 17 patients who were studied before and after streptokinase were classified as acute and three as subacute progressive major pulmonary embolism. Eight showed marked angiographic improvement, four moderate and two slight angiographic improvement. There was a moderate and statistically significant fall in the mean pulmonary arterial pressure and pulmonary vascular resistance. In addition, all seven patients in whom no angiographic improvement occurred during heparin therapy showed moderate or marked angiographic improvement after a further 24 hours of treatment with streptokinase. The results strongly suggest that streptokinase therapy accelerates thrombolysis in patients with acute major pulmonary embolism.

Acute Disease↗

PubMed1983

Systemic fibrinolytic activity and inhibitor levels during treatment of deep vein thrombosis with urokinase and streptokinase.

In a prospective, randomized trial 33 patients with deep vein thrombosis were treated either with 2,200 or 1,100 IU/kg/h urokinase or with 100,000 IU/h streptokinase for at least 6 days. While streptokinase was given continuously, urokinase was administered intermittently (12 hr urokinase alternating with 12 hr heparin). Urokinase treatment resulted in a dose-dependent fibrinolytic state with shortening of the euglobulin clot lysis time, easily demonstrable amidolytic activity and moderate decrease of plasminogen. At the end of each urokinase-free interval the fibrinolytic activity had mostly faded, but was reproducibly elicited again by each new urokinase administration. Streptokinase immediately evoked the customary, intense fibrinolytic state, which progressively tapered off as plasminogen fell to 1% of its pretreatment concentration. In all treatment groups alpha-2-antiplasmin dropped to approximately 40% of its initial value during the first 12 hr with a further decrease to about 20% after 6 days. alpha-2-macroglobulin fell only moderately with either urokinase regimen, whereas it decreased progressively to 45% under streptokinase. While the fibrinolytic activity decreased under streptokinase over the 6-day infusion period, it appeared to increase with each successive urokinase infusion particularly with 1100 IU/kg/h. Thus the final euglobulin clot lysis times and the final fibrinogen concentrations were similar in all three treatment groups on the sixth day.

Blood Coagulation Tests↗

PubMed1983

[Immobilization of the human plasmin light chain and analysis of its complexes with streptokinase].

The heavy and light chains of human plasmin were separated by affinity 1-lysin-cellulose column chromatography. The S-carboxymethyl light chain derivative of human plasmin was imobilized by aminogroups by the insoluble matrices. Insoluble derivatives cf plasmin light chain retain an insignificant proteolytic activity, human plasminogen activator activity and capacity to form complexes with streptokinase. The activator activity of the immobilized light chain-streptokinase complex increases 5-10-fold with respect to the human plasminogen. When adding the light chain preparation to immobilized streptokinase its activator activity relative to the human plasminogen is twice as high. The both complexes: immobilized light chain-streptokinase and light chain-immobilized streptokinase are stable and may be reused for plasminogen activation.

Chromatography, Affinity↗

PubMed1984

Anaphylactic reactivity to streptokinase.

Streptokinase is used worldwide as a thrombolytic agent. Allergic reactions have been observed to streptokinase; however, the immunologic mechanisms have not been described. In a case of an anaphylactic reaction to intravenously administered streptokinase during the evolution of a myocardial infarction, the patient had elevated specific IgE and IgG levels to this agent demonstrated by in vitro methods. In vivo testing demonstrated cutaneous immediate-type hypersensitivity with a typical wheal and flare reaction. Critically ill patients receive short-term treatment with streptokinase. Because of the potential danger of anaphylaxis in these patients, we provide an approach that may identify those at risk. The urgency of the requirement for immediate administration of streptokinase is such that an in vitro test cannot be used; thus, results of appropriate skin testing must be evaluated.

Anaphylaxis↗

PubMed1983

[Streptokinase immobilization in insoluble carriers, and properties of the immobilized protein].

Immobilization of streptokinase was performed by bromine cyan-activated cellulose and by aminoethyl cellulose using glutaric aldehyde and N-cyclohexyl-N'-[2-(4-morpholinyl)-ethyl-carbodiimide. The specific activator activity of the immobilized streptokinase is 70-100% of that of free streptokinase. In multiple application of the immobilized protein preparations streptokinase obtained by bromine cyan-activated cellulose is the most stable: it retains more than 40% of initial activity after 10 repeated applications. The immobilized streptokinase is shown to be more thermostable as compared to the soluble one.

Cellulose↗

PubMed1983

Response of an abdominal aortic thrombotic occlusion to local low-dose streptokinase therapy.

Local low-dose streptokinase infusion (5000 to 6000 IU/hr) as compared to systemic streptokinase infusion (loading dose 250,000 IU/hr, maintenance dose 100,000 IU/hr) successfully relieved a total thrombotic abdominal aortic occlusion. No complications of bleeding or distal embolization occurred during streptokinase therapy, which required only 8 days of hospitalization. When seen at 4 months after streptokinase infusion, the patient was still free of symptoms. When no immediate threat of ischemic limb loss exists, streptokinase may offer a promising therapeutic alternative to surgical intervention for patients who represent a poor operative risk.

Aorta, Abdominal↗

PubMed1980

[First results of emergency treatment in massive fulminant lung embolism by means of a rapidly injected streptokinase in a high initial dose (author's transl)].

Five cases of patients with massive fulminant lung embolism are reported who were successfully reanimated in spite of one or several cardiac arrests by bolus injection of 750,000 to 1,000,000 I.U. streptokinase applicated intraveneously within a few seconds up to about 3 min. The effect of this rapidly injected high initial dose of streptokinase on the embolus in the A. pulmonalis and on the disturbed microcirculation in prefinale states of shock is discussed. In consequence of the aggressive therapy with streptokinase severe haemorrhagic complications occurred in all cases reported. As the patients would not have survived the massive fulminant lung embolism without this therapy it is concluded that in certain cases of fulminant lung embolism the bolus injection of streptokinase should be tried besides other measures of reanimation as a ultima ratio in spite of a contraindicated lysis. We think that this aggresive therapy is indicated for patients with massive fulminant lung embolism who were treated in a conventional way without success, who could not be operated or who had already suffered from a cardiac arrest. It is suggested to treat a massive fulminant lung embolism not only with conventional measures of reanimation but also with rapid i.v.-injection of 750,000 to 1,000,000 I.U. of streptokinase.

Adult↗

PubMed1982

Streptokinase of heparin in the treatment of deep vein thrombosis. Follow-up results of a prospective study.

In a previous study on 42 patients with acute deep vein thrombosis, randomly allocated to treatment with streptokinase or heparin, we found that 71.4% of the streptokinase-treated patients achieved phlebographically significant thrombolysis as compared to 23.8% in the heparin group. These patients have been reevaluated after a mean observation period of 6 1/2 years. Seven patients had died and there were no other drop-outs. Thus, 35 patients were subjected to the follow-up study consisting of phlebography and clinical examination. The evaluations were performed without knowledge of the initial therapy. Seven patients had phlebographically normal veins, and all belonged to the streptokinase group. This difference between the treatment groups is statistically highly significant (p less than 0.01). At clinical examination, 13 of the 17 patients in the streptokinase group had normal legs and 4 exhibited moderate postthrombotic changes. In contrast, 3 of the heparin-treated patients showed serious postthrombotic changes with open leg ulcers, and only 6 of 18 patients in this group had normal legs. The present results strongly support the assumption that streptokinase therapy is the best treatment at present in patients with acute deep vein thrombosis. This has been shown for the initial thrombolysis, and now also for the avoidance of late postthrombotic changes.

Adult↗

PubMed1994

Characterization of a novel streptokinase produced by Streptococcus equisimilis of non-human origin.

Streptokinases are proteins with plasminogen activator activity produced by certain hemolytic streptococci. We previously identified equine streptococcal isolates which produced streptokinases (ESKs) that bound both human and equine plasminogen but only readily activated equine plasminogen (14). This property was exploited to purify a representative ESK produced by Streptococcus equisimilis strain 87-542-W. Affinity chromatography with human plasminogen resulted in the isolation of a M(r) approximately 49,000 molecule with two isoforms. This ESK was subsequently compared to well characterized streptokinases (HSKs) that efficiently activate human plasminogen. Differences in streptokinases were identified in the highly conserved amino-terminal amino acid sequence, peptide maps, and antigenic properties, and these differences were supported by DNA hybridization studies. These results indicate that the family of proteins identified as streptokinases has much greater diversity than previously appreciated.

Amino Acid Sequence↗

PubMed1993

Acute myocardial infarction survival rate and complications after streptokinase therapy in Hospital Universiti Sains Malaysia, Kelantan--a comparative study.

Thrombolytic therapy is a well-established therapy in acute myocardial infarction (AMI), reducing mortality and infarct size. This study is a retrospective analysis of survival and complications after the use of streptokinase at Hospital Universiti Sains Malaysia. Streptokinase was first used here in March 1990. Between then and February 1992, 126 patients were admitted to the Coronary Care Unit. Thirty-two patients who fulfilled our criteria for thrombolytic treatment were given an hour intravenous infusion of 1.5 MU streptokinase, and started on aspirin. A control group of 64 patients selected from before March 1990, and matched for age, sex and site of infarct, was given standard therapy. The survival at 4 weeks post-AMI was 91% in the streptokinase therapy group and 91% in both groups (p > 0.05). The complications encountered were reperfusion arrhythmias (2 patients), hypotension(1), maculopapular rash(1) and gum bleeding(1). None of these complications were statistically increased when compared to the control group and none resulted in the death of a patient. We conclude that streptokinase therapy can be given safely in a rural Malaysian setting. Our survival and complication rates are comparable with other published series.

Adult↗

PubMed1977

[Investigations of the clinical course of acute myocardial infarction. I. The fibrinolytic treatment of acute myocardial infarction with streptokinase (author's transl)].

In 26 hospitals a study was carried out to investigate the influence of fibrinolytic therapy on mortality in hospital in acute myocardial infarction. The study was concerned with the question whether fibrinolytic therapy in acute myocardial infarction could lower the hospital mortality and whether fibrinolytic therapy should be recommended as an additional therapy for any type of hospital, irrespective individual differences in treatment. 483 out of 1463 patients were treated with streptokinase. These patients were randomized in two groups. Group I was treated in the usual way additionally streptokinase was given, group II without streptokinase. Both groups were similar regarding the course of illness and clinical data. It could be shown that the mortality was not significantly lowered by streptokinase. But in case of shock the mortality seemed to be lower after streptokinase, this difference not being significant.

Acute Disease↗

PubMed1993

A study of the use of the thromboxane A2 antagonist, sulotroban, in combination with streptokinase for local thrombolysis in patients with recent peripheral arterial occlusions: clinical effects, platelet function and fibrinolytic parameters.

In peripheral thrombolysis adjuvant anti-platelet therapy may help to lyse otherwise resistant thrombus, thereby increasing the number of patients successfully treated and reducing the "time to lysis". If continued after lysis it may help to prevent early rethrombosis. In this pilot study 21 patients undergoing peripheral thrombolysis with streptokinase were randomised to receive the thromboxane receptor antagonist sulotroban or placebo. The dose of sulotroban given was 2 mg/min (four patients), 4 mg/min (five patients) or 8 mg/min (four patients), eight patients received placebo. The clinical and laboratory effects of the treatment were monitored. Thrombolysis was achieved more quickly in patients receiving sulotroban, however, there was no difference between groups in the number of patients in whom recanalisation was achieved (six of eight receiving placebo and eight of 13 receiving sulotroban) or in the number of cases of early rethrombosis. During lysis there was an increase in plasma beta-thromboglobulin with similar levels being found in patients receiving sulotroban and streptokinase and those receiving streptokinase alone. No other major changes in platelet function during lysis were seen in patients receiving streptokinase alone. Sulotroban significantly reduced platelet aggregation and 14C-5HT release in response to several platelet agonists. With the thromboxane mimetic U46619 the degree of inhibition of aggregation and 14C-5HT release depended on the dose of sulotroban used. High levels of inhibition were associated with an excess of haemorrhagic complications especially in combination with a low plasma fibrinogen level. We conclude that the use of low dose sulotroban in combination with streptokinase merits further study and may hve a role in accelerating lysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

[Favorable long-term results of primary percutaneous transluminal coronary angioplasty in acute myocardial infarction compared to intravenous streptokinase treatment; a randomized study].

OBJECTIVE: To evaluate the treatment of patients with acute myocardial infarction with thrombolytic drugs or primary angioplasty in a randomized trial. DESIGN: Randomized trial. SETTING: Hospital De Weezenlanden, Zwolle, the Netherlands. METHODS: A total of 301 patients with acute myocardial infarction were included in the trial, of whom 152 patients were allocated to primary angioplasty and 149 patients to intravenous streptokinase. The mean follow-up duration was 31 months (SD:9). Left ventricular function was assessed with a radionuclide technique before hospital discharge and at the end of the follow-up period. A cost analysis was performed based on the calculation of all medical costs. RESULTS: At the end of the follow-up period, 5% of the angioplasty patients had died from a cardiac cause compared with 11% of the patients randomized to intravenous streptokinase (p = 0.031). Death or non-fatal reinfarction occurred in 7% of angioplasty patients and in 28% of streptokinase patients (p < 0.001). There was a sustained beneficial effect of angioplasty in comparison with streptokinase on left ventricular function, 48 (SD12)% versus 43(SD13)% (p < 0.01). Most benefit was observed in patients with an anterior wall myocardial infarction. CONCLUSION: After an average of 31 months (SD:9) primary angioplasty in comparison with intravenous streptokinase resulted in a lower rate of cardiac death and reinfarction and a better left ventricular ejection fraction, without an increase in total costs.

Angioplasty, Balloon, Coronary↗

PubMed1996

A paradox of thrombogenesis by streptokinase and its prevention by iloprost and camonagrel.

Here we report that streptokinase is responsible for forming thrombi both in vitro on blood-superfused endothelial cells of rabbit aorta and in vivo on blood-superfused collagen strips in extracorporal circulation of anesthetized cats. This short-lasting paradoxical thrombogenic phase is followed by the expected long-lasting thrombolysis. The biphasic action of streptokinase occurred in vitro at concentrations of 100-2000 U/ml and in vivo at doses of 1000-3000 U/kg i.v. Both phases are mediated by endogenous plasmin as evidenced by deleting the streptokinase-induced thrombogenesis and thrombolysis following pretreatment with epsilon-aminocaproic acid or aprotinin. On the other hand, selective block of the paradoxical thrombogenesis was achieved after pretreatment with camonagrel, a thromboxane synthase inhibitor which raises plasma levels of endogenous prostacyclin, or with iloprost, a stable analog of prostacyclin. It is suggested that endogenous or exogenous prostacyclin inhibits activation of platelets by plasmin, and hence the thrombogenesis by streptokinase is abolished, while the beneficial thrombolytic action of streptokinase is augmented.

Animals↗

PubMed1996

Use of streptokinase in four dogs with thrombosis.

Four dogs with thrombosis were referred for diagnostic testing and were subsequently treated by the use of streptokinase. The range of duration of clinical signs associated with thrombosis was 6 to 120 days. Causes of thrombosis were heart disease (1 dog), protein-losing nephropathy and hyperadrenocorticism (1), hyperadrenocorticism (1), and idiopathic (1). Possible factors that predisposed dogs to hypercoagulability included hypertension (2 dogs) and diabetes mellitus (1). All dogs were treated for underlying disease by use of supportive care. The first dog was treated with a loading dose of 250,000 U of streptokinase, i.v., with a subsequent maintenance dosage of 100,000 U/h, i.v., and also was treated with anticoagulant. The subsequent 3 dogs were treated with a loading dose of 90,000 U of streptokinase, i.v., and maintenance dosage of 45,000 U/ h, i.v., at various intervals. These dogs also were treated with anticoagulant. Three dogs had minor hemorrhage as an adverse effect to streptokinase infusion, but they did not require treatment for the hemorrhage. Complete resolution of the thrombus was observed in 3 dogs, and partial resolution of the thrombus was observed in the other dog. In all dogs, partial or complete resolution of clinical signs associated with thrombosis was seen. Streptokinase may be an effective treatment for dogs with thrombosis.

Adrenocortical Hyperfunction↗

PubMed1979

[Immunological concentration determinations of the streptokinase preparation Awelysin dissolved in various infusion solutions for its stability evaluation].

By means of the electro-immuno-assay according to Laurell the decrease of concentration was determined for the streptokinase preparation Awelysin dissolved in various infusion media at 20 degrees C. The stability behaviour of a streptokinase solution of 1.000 IE/ml showed a significant decrease of concentration after 24 hours (alpha less than 5%) as compared with the initial concentration. However, in comparison no significant differences as to the streptokinase stability could be found by using different infusion solutions. At 20 degrees C the decrease of streptokinase concentration may be neglected up to 24 hours in an infusion solution of streptokinase previously prepared.

Drug Stability↗