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Acute massive pulmonary embolism treated with streptokinase during labor and the early puerperium.

Acute massive pulmonary embolism occluding 60-70% of the pulmonary circulation occurred in a young primipara during the 28th week of pregnancy. She was critically ill despite 40 h of heparin infusion and thrombolytic therapy with streptokinase was initiated. After a 10-h infusion she went into labor and streptokinase treatment was stopped. One hour later she gave birth spontaneously to a preterm infant in footling breech delivery. The infant did well neonatally. Streptokinase infusion was recommenced 8 h after delivery. Because of increasing blood loss on the second day after delivery, streptokinase was withdrawn after a total treatment time of 29 h. Total hemorrhage amounted to 8.9 litres. Serial perfusion lung scans showed complete resolution of the emboli and normal lung function was restored.

Acute Disease↗

Effect of ticlopidine on streptokinase-induced thrombolysis in rats.

Using our original assay system we found that ticlopidine (TP, 30 mg/kg i.v.) had produced a prompt thrombolysis of preformed clots in extracorporeal circulation of anaesthetized rats. In contrast with ticlopidine streptokinase (SK, 30,000 U/kg i.v.) proved thrombogenic for an initial period of 10-30 min, followed only later by the expected thrombolytic action. In ticlopidine pretreated rats the thrombogenic effect of streptokinase was eliminated, and its thrombolytic potency intensified. This is the first experimental support for a conception that a combined therapy with ticlopidine and streptokinase may restrict the "early hazard" associated with streptokinase therapy.

Animals↗

[Thrombopenia and acute renal insufficiency after treatment with streptokinase. Role of steroids].

Proteinuria is common after streptokinase treatment. An immunological mechanism in the renal glomerulus has been suggested to explain this side effect. However, thrombopenia and acute renal failure streptokinase induced are uncommon. We present a case of thrombopenia and acute renal failure after streptokinase administration for myocardial infarction that improved with steroid therapy. We discuss the probable pathophysiology of these adverse effects of streptokinase and the potential usefulness of steroids in its prevention and treatment.

Acute Kidney Injury↗

Accelerated infusion of streptokinase in acute myocardial infarction results in better TIMI flow grade in infarct-related artery.

Bolus followed by rapid infusion of tissue plasminogen activator results in higher grade of TIMI flow in infarct-related artery as compared to slow infusion. In the present study, an accelerated regimen of streptokinase given over 15 minutes was compared with conventional infusion over one hour in 47 patients presenting within 12 hours of acute myocardial infarction. Forty-seven patients (44 males, 3 females; mean age 54.0 +/- 1.1 years) were randomly allocated to receive 1.5 million units of streptokinase either over 15 minutes (group 1, n = 24) or over one hour (group 2, n = 23) at a mean interval of 5.4 +/- 3.6 hours after onset of symptoms. All the patients received aspirin and intravenous heparin (1000 U/hr) for 96 hours after thrombolysis. Coronary angiography was performed in 43 patients (22 in group 1, 21 in group 2) prior to discharge from the hospital (mean 7 +/- 2.1 days after acute myocardial infarction) and patency of the infarct-related artery and grade of TIMI flow were determined. Infarct-related artery was patent (TIMI 2/3 flow) in 19 (86.4%) patients in group 1 as compared to 12 (57.1%) in group 2 (p < 0.05). TIMI grade 3 flow in the infarct-related artery was present in 13 (59.1%) in group 1 as compared to 7 (33.3%) in group 2 (p = 0.1). There was no significant difference between group 1 and 2 in time of presentation (mean 5.3 +/- 3.9 hrs vs 5.5 +/- 3.2 hrs), time to needle in hospital (25.6 +/- 11.2 min vs 26.3 +/- 6.2 min), site of infarct (anterior myocardial infarction 12 in group 1 vs 11 in group 2), relief of pain at 90 min (13 vs 12), more than 50 percent reduction of ST elevation at 90 minutes (17 vs 12) and left ventricular ejection fraction (48.8 +/- 9.1% vs 49.8 +/- 16.0%), respectively. Streptokinase was well tolerated in both the groups, although hypotension was more common with the accelerated regimen (5 in group 1 vs 3 in group 2; p = NS). Thus, 'accelerated' streptokinase given over 15 minutes in patients presenting within 12 hours of acute myocardial infarction is well tolerated and results in higher grades of TIMI flow in the infarct-related artery as compared to the "conventional" one-hour infusion regimen.

Adult↗

[Structure-functional change in streptokinase exposed to ultrasound].

To optimize conditions of acousto-enzymatic thrombolysis the influence of low-frequency ultrasound on the isolated preparation of streptokinase was investigated. The ultrasound treatment with intensity 26 W/cm2 at 37 degrees C within 5-10 minutes was not accompanied by changes of structure-functional properties of the streptokinase molecule. Increase of ultrasound-processing time (10-60 minutes) resulted in non-covalent hydrophobic aggregation of some part of the protein. In contrast to native protein ultrasound modified streptokinase is readily degraded by plasmin with formation of polypeptide fragments with molecular weights ranged from 43 up to 14 kD. The processes of aggregation and increased proteolytic degradation resulted in lower efficiency of plasmin autoactivation under the action of sounded streptokinase.

Chromatography, High Pressure Liquid↗

Biochemical changes noted during intermittent administration of streptokinase.

An intermittent dosage scheme of streptokinase (standard initial dose 600,000 units SK infused over 30 min and repeated injections of 250,000 units SK at 24 hr intervals) was applied during 4 days in 9 patients with chronic obliterative arterial disease and in 8 patients with venous occlusion. Each dose of streptokinase produced an immediate fall in plasminogen to 17% (SEM 5.1) of the initial value, the level then rose to 50% (SEM 5.4) within 24 hr. Lowered levels of antiplasmin and fibrinogen (both less than 40% of the initial values) were maintained. This safe level of fibrinogen was maintained despite brief but high peaks of plasmin activity after each injection of SK. A parallel increase of the thrombin time and the fibrin (ogen) degradation products was obtained following each infusion. No bleeding was observed. The relative therapeutic effect of intermittent infusions of streptokinase has still to be compared with the continuous administration of streptokinase in controlled clinical trials.

Antibodies↗

Evaluation and comparison of the adverse effects of streptokinase and alteplase.

The frequency and severity of adverse effects resulting from the administration of streptokinase and alteplase were determined in 126 consecutive patients who received standard dosages of these agents for the treatment of acute myocardial infarction. Evaluation was based on patient assessment by nursing staff, physicians, and the investigators before, during, and after thrombolytic administration. Overall, adverse effects occurred in 15 (41.7%) of 36 patients receiving streptokinase and 12 (13.3%) of 90 receiving alteplase (p = 0.001). No major bleeding or neurologic events were documented. Minor bleeding occurred in 13.9% and 7.8% of streptokinase and alteplase recipients, respectively (p = 0.47), and hypotension in 8 (22.2%) and 5 (5.6%), respectively (p = 0.01). The frequency of hypotension associated with streptokinase was significantly higher than that with alteplase. Thrombolytic-induced hypotension was easily managed and was not associated with sequelae.

Adult↗

Control of streptokinase gene expression in group A & C streptococci by two-component regulators.

BACKGROUND & OBJECTIVES: Group A streptococci (GAS) and human isolates of group C streptococci (GCS) have the stable capacity to produce the plasminogen activator streptokinase, albeit with varying efficiency. This property is subject to control by two two-component regulatory systems, FasCAX and CovRS, which act as activator and repressor, respectively. The present work aims at balancing these opposing activities in GAS and GCS, and at clarifying the phylogenetic position of the FasA response regulator, the less understood regulator of the two systems. METHODS: The GCS strain H46A and GAS strain NZ131 were used. Escherichia coli JM 109 was used as host for plasmid construction. Streptokinase activity of various wild type and mutant strains was measured. Phylogenetic trees of streptococcal FasA homologues were established. RESULTS: The streptokinase activities of the GAS strain NZ131 and the GCS strain H46A were attributable to more efficient CovR repressor action in NZ131 than in H46A. The FasA activator, on the other hand, functioned about equally efficient in the two strains. Phylogenetically, FasA homologues clustered distinctly in the proposed FasA-BlpR-ComE family of streptococcal response regulators and used the LytTR domain for DNA binding. INTERPRETATION & CONCLUSION: Assessing the apparent streptokinase activity of streptoccal strains require the dissection of the activities of the cov and fas systems. Although experimental evidence is still missing, FasA is closely related to a widely distributed family of streptococcal response regulators that is involved in behavioral processes, such as quorum sensing.

Amino Acid Sequence↗

[Effect of streptokinase on the content of plasminogen activator inhibitor of type 1].

The influence of streptokinase on plasminogen activators inhibitor of type I (PAI-1) was investigated with the use of model systems in vitro and in vivo. It was defined, that intravenous streptokinase injection causes an increase in PAI-1 content in mammals' blood plasma. Experiments in vitro have shown that the increase in PAI-1 concentration takes place as a result of streptokinase action. It occurs due to platelets activation with subsequent PAI-1 secretion from their a-granules. It is established, that PAI-1 is secreted by platelets both in free and in complex forms. The data obtained in the work, allow to assume, that the simultaneous substantial increase in PAI-1 content with platelets activation, as a result of streptokinase influence, can lead to new thrombotic complications risk.

Animals↗

Intracoronary streptokinase in unstable angina: a prospective randomised study.

Results of our prospective, randomised pilot trial to evaluate the clinical effects and the angiographic correlates of early thrombolysis in patients with unstable angina are reported. Sixty-seven patients had coronary angiography 10 +/- 8 (median 7) hours after an episode of transient chest pain at rest with reversible ischaemic changes on the electrocardiogram. Patients with left main disease (4), or diffuse coronary disease and unidentified ischemia-producing lesions (13) were excluded, as were those without severe (greater than or equal to 70%) stenosis (10). Intracoronary thrombus was identified at angiography in 7 patients (17%) and complex coronary lesions in 5 (12%) of the remaining 40 patients who were randomised to either intracoronary streptokinase 250,000 IU followed by intravenous heparin along with conventional treatment (20 patients), or to conventional treatment alone (20 patients). All patients received Aspirin. No differences between the streptokinase and the conventional treatment groups were observed with respect to demographic and clinical characteristics at admission to the study. During observation in the intensive care unit for 3 +/- 1 days, 8 patients (40%) with streptokinase and 10 (50%) with conventional treatment were free from angina and infarction (p = 0.75; 95% confidence interval for the difference in response rates = -20 to 40%). There were no bleeding complications and no patient died. Patients enrolled in our study had fewer coronary thrombi at angiography than currently reported. Our data did not show that adjunct treatment with streptokinase and heparin is superior to conventional treatment alone in these patients.

Aged↗

[The thrombolytic activity of acylated activator complexes of plasmin-streptokinase with different rates of reactivation].

In the experiments on guinea-pigs with venous thrombosis there were studied the fibrin- and thrombolytic effects of streptokinase, the plasmin-streptokinase complex and the acylated derivatives of the complex with various rates of reactivation. It was established that the acylated derivatives of the plasmin-streptokinase complex possess greater stability in the blood flow and lead to more prolonged stimulation of fibrinolysis at less magnitude of its systemic activation. Due to this the acylated derivatives of the plasmin-streptokinase complex produce less pronounced fibrinogenolysis. In connection with a high affinity to fibrin their thrombolytic action does not depend on the systemic activation of fibrinolysis.

Animals↗

[Modification of functional groups of the streptokinase molecule during photooxidation].

Photochemical oxidation with methylene blue as photosensitizer results in the destruction of one histidine residue in the streptokinase molecule. This process is characterized by the rate constant corresponding to the modification of free L-histidine and results in partial inactivation of the protein. The rate of protein photo oxidation and photoinactivation is pH-dependent. As can be judged from the results of CD spectroscopy and gel chromatography, in weakly acidic (but not in weakly alkaline) media the reaction results in conformation changes of the streptokinase globule which affect the state of the protein tryptophanyl residue. It was found that the imidazole group destroyed during the photooxidation reaction is not essential either for the specific activity of streptokinase or for the formation of is stable complex with human plasminogen. The specificity of modification of the streptokinase histidine residue during the photooxidation reaction is discussed.

Chromatography, Gel↗

Acylated plasminogen-streptokinase activator complex: a new approach to thrombolytic therapy.

Acylated plasminogen-streptokinase activator complex (APSAC; antistreplase) is an inactive complex of human plasminogen and streptokinase. When it is injected, a controlled deacylation of the catalytic center occurs, activating the complex so that thrombolysis may begin. This process extends the half-life of streptokinase, allowing for 4-6 hours of fibrinolytic activity. Anistreplase has demonstrated equivalent efficacy to intracoronary streptokinase with regard to reperfusion rates in acute myocardial infarction. In addition, patients have shown a 56% reduction in mortality at 28 days with anistreplase compared to heparin. The adverse effect profile of anistreplase includes minor bleeding and hematoma formation at the site of venipuncture, hypotensive and bradycardic episodes, arrhythmias, facial flushing, fever, and rarely, allergic reactions. Serious bleeding reactions are uncommon, with the frequency of cerebrovascular accident reported at 0.4-0.6%. The special advantage of anistreplase is its administration as a 30-U intravenous bolus injected over 5 minutes, eliminating the need for long infusions and increasing the ease of administration. Based on its efficacy and ease of administration, anistreplase may become the drug of choice in the emergency treatment of acute myocardial infarction.

Anistreplase↗

Intravenous streptokinase in acute evolving myocardial infarction--six to thirty-six months follow up.

270 consecutive patients who presented within six hours of the onset of acute myocardial infarction (AMI) and had no contraindication to thrombolytic therapy received intravenous infusion of 750,000 units of streptokinase (STK) in thirty minutes followed by heparin and oral anticoagulants. Treatment was instituted within 210 +/- 64 minutes after the onset of symptoms and reperfusion was achieved in 44 +/- 21 minutes. Reperfusion was recognised by indirect criteria in 249 patients, (92.2%) in the 0-6 hours group and 100% in the 0-3 hours group in all 72 patients. 2D echo LV ejection fraction (LVEF) improved from 51.6% +/- 9.4% at 0 hours to 60.61 +/- 8.4% at first week. In 40 patients (14.8%) there was early reocclusion in mean time of 36 +/- 13 hours of treatment. The incidence of reocclusion was higher in patients with anterior wall AMI than with inferior wall AMI. Reocclusion was also more frequent in patients who were administered adjuvant Dipyridamole therapy. In 36 of these patients reperfusion was achieved with an additional dose of streptokinase. During the last thirty-six months follow up, treadmill stress test was positive in 15 out of 80 (18.8%) streptokinase group subjected to it as compared to 42.2% conventionally managed patients. No LV thrombus, aneurysm or papillary muscle dysfunction was seen. 25 patients (9.2%) underwent coronary angiography six weeks later. CABG was undertaken in only 18 patients (6.6%) along with endarterectomy in one (.37%). None of the patients required additional aneurysmectomy or valve replacement. Elderly patients (above 75 years) suffered major haemorrhagic complications (.37%) and 17% of patients had minor bleeds. In-hospital mortality was 4.8% as compared to 10.2% in the control group (P less than .05). A long-term follow-up (6-36 months) revealed 11 patients that (4.07%) had reinfarction at mean time of 18 +/- 11 months (P less than .05). The late mortality rate in 6-36 months follow up was was 1.8% (P less than .05). It was concluded that intravenous streptokinase in acute myocardial infarction along with long-term anticoagulants is safe and effective. It reduces early and late mortality and morbidity significantly. A conservative strategy of subjecting patients to CABG after effective thrombolysis was found satisfactory during six to thirty-six months follow-up.

Adult↗

[Allergic reactions during streptokinase therapy].

The article reviews immunological reactions to streptokinase. The humoral immune response to streptokinase involves antibodies of different subclasses, including IgG, IgM, and IgE. A T cell response to streptokinase can also be demonstrated, involving both CD4 and CD8 positive cells. Streptokinase therapy involves increased risk of all kinds of allergic reactions, including urticaria, bronchial obstruction, shock and serum sickness.

Humans↗

[Evaluation of the effectiveness of streptokinase in acute myocardial infarct with respect to the pump function of the heart].

During 2 years and 3 months 230 patients suffering from acute myocardial infarction were treated at an Intensive Care Unit and a Department of Cardiology. Streptokinase was given intravenously to 54 of them. Out of 54 patients, in 52% the localisation of the myocardial infarction was in the anterior and in 48% in the posterior wall. The patients were divided in the three categories according to the onset of symptoms: up to 2 hours, 2-4 hours and 4-6 hours. The dose of streptokinase was 1,500,000 i.u. during 1.5 hours. The CPK and MBCPK level reached the maximum values up to 12 hours and was to lowest in the first group. In 74% of the patients the serum enzyme level showed successful reperfusion of a coronary artery. Electrocardiographic findings of a successful myocardial reperfusion amounted to 36% in the first, 40% in the second, and 17% in the third group. Malignant ventricular arrhythmias appeared in the first group in 3.6%, in the second in 12.5% and in the third group in 14.2%. The criteria for successful myocardial reperfusion by echocardiography (analysed regional wall motion) were present in 52% in the first, in 50% in the second, and in 17% in the third group. Coronarography and ventriculography were performed in 17 patients after 21 days of treatment, with successful results in 88% (15 out of 17 patients). In a group of 176 patients unable to be treated with streptokinase because of the onset of symptoms of myocardial infarction (more than 6 hours) or because of contraindications for that treatment, the lethality rate reached 17.6%. The lethality rate in the group of 54 patients treated with streptokinase was 5.5%. Local complication (hemorrhage) during the treatment was observed in one patient (2%).

Heart↗

[Thrombolytic therapy with ultra-high doses of streptokinase].

Two pilot studies were carried out in patients suffering from acute myocardial infarction. They received high doses of streptokinase and acylated streptokinase-plasminogen activator complex intravenously as a bolus injection. Furthermore, the possibility of using streptokinase bolus therapy was examined in patients with acute vascular occlusion. Due to the limited number and the heterogenicity of cases the results obtained in patients with acute myocardial infarction are to evaluate with some reservation. In patients with acute vascular occlusion streptokinase bolus therapy at high doses proved to be a promising alternative to the conventional therapy.

Coronary Angiography↗

[Short-term lysis of venous thrombosis with ultra-high streptokinase doses].

11 patients with deep pelvic and leg vein thrombosis were treated with ultra-high streptokinase infusion, 1.5. 10(6) IE streptokinase per hour over a six hour period. Opening of the vein occlusion was achieved in four cases completely and in five cases partially. The frequency of complications was lower at short-time thrombolysis with ultra-high streptokinase infusion in contrast to long-time thrombolysis. Bleedings did not occur. Because of the slight side effects ultra-high streptokinase infusion is an alternative in the fibrinolytic treatment of risk patients with pelvic and leg vein thrombosis.

Adult↗