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PubMed1997

Randomised controlled trial of intrapleural streptokinase in community acquired pleural infection.

BACKGROUND: Standard treatment for pleural infection includes catheter drainage and antibiotics. Tube drainage often fails if the fluid is loculated by fibrinous adhesions when surgical drainage is needed. Streptokinase may aid the process of pleural drainage, but there have been no controlled trials to assess its efficacy. METHODS: Twenty four patients with infected community acquired parapneumonic effusions were studied. All had either frankly purulent/culture or Gram stain positive pleural fluid (13 cases; 54%) or fluid which fulfilled the biochemical criteria for pleural infection. Fluid was drained with a 14F catheter. The antibiotics used were cefuroxime and metronidazole or were guided by culture. Subjects were randomly assigned to receive intrapleural streptokinase, 250,000 i.u. daily, or control saline flushes for three days. The primary end points related to the efficacy of pleural drainage--namely, the volume of pleural fluid drained and the chest radiographic response to treatment. Other end points were the number of pleural procedures needed and blood indices of inflammation. RESULTS: The streptokinase group drained more pleural fluid both during the days of streptokinase/control treatment (mean (SD) 391 (200) ml versus 124 (44) ml; difference 267 ml, 95% confidence interval (CI) 144 to 390; p < .001) and overall (2564 (1663) ml, 95% CI 465 to 2545; p < 0.01). They showed greater improvement on the chest radiograph at discharge, measured as the fall in the maximum dimension of the pleural collection (6.0 (2.7) cm versus 3.4 (2.7) cm; difference 2.9 cm, 95% CI 0.3 to 4.4; p < 0.05) and the overall reduction in pleural fluid collection size (p < 0.05, two-tailed Fisher's exact test). Systemic fibrinolysis and bleeding complications did not occur. Surgery was required by three control patients but none in the streptokinase group. CONCLUSIONS: Intrapleural streptokinase probably aids the treatment of pleural infections by improving pleural drainage without causing systemic fibrinolysis or local haemorrhage.

Community-Acquired Infections↗

PubMedDate not supplied

Negative interaction of aspirin and streptokinase in acute ischemic stroke: further analysis of the Multicenter Acute Stroke Trial-Italy.

BACKGROUND: Thrombolytic therapy improves the functional outcome in acute ischemic stroke, but the risk of death and cerebral hemorrhage remains high. Aspirin given together with a thrombolytic agent may worsen the risk-to-benefit ratio. We performed a further Multicenter Acute Stroke Trial-Italy (MAST-I) which is the only randomized, controlled trial that has tested the effect of this combination to evaluate the risk of aspirin use plus streptokinase. PATIENTS AND METHODS: We made a post hoc analysis of the MAST-I results comparing streptokinase plus aspirin (156 patients) with streptokinase alone (157 patients). We evaluated the risk of death and cerebral hemorrhage. RESULTS: The combined regimen significantly increased early case fatality from day 3-10 (53 vs. 30; OR 2.1; CI 1.2-3.6). The death excess was solely due to treatments and was not explained by the main prognostic predictors (multifactorial analysis). The cause of death in the combination group was mainly cerebral (42 vs. 24; OR 2.0; CI 1.3-3.7) and associated with hemorrhagic transformation (22 vs. 11; OR 2.2; CI 1.0-5.0). The rate of stroke reoccurrence was not increased in patients treated with streptokinase alone (15 vs. 11; OR 1.4; CI 0.6-3.4). CONCLUSIONS: Stroke patients treated with streptokinase plus aspirin have an increased risk of early death, probably due to cerebral hemorrhagic complications. Whenever thrombolytics are chosen for acute stroke treatment, aspirin and other antiplatelet agents should be avoided.

Acute Disease↗

PubMedDate not supplied

Reduction of surgery-induced peritoneal adhesions by continuous release of streptokinase from a drug delivery system.

Postoperative abdominal adhesions may lead to intestinal obstruction and infertility. The effect of continuous release of streptokinase to the peritoneal cavity on postoperative adhesions was examined under experimental conditions. Peritoneal adhesions were induced in rats and the animals were further treated by intraperitoneal administration of streptokinase solution, polyhydroxybutyrate-co-hydroxyvalerate (PHBV) membrane alone and streptokinase loaded PHBV membrane and compared to sham operated and untreated groups. Formation of adhesions was evaluated by quantitative macroscopic grading, histopathologically with light microscopy, on the following week. Streptokinase loaded PHBV prevented postoperative adhesion formation in 90% of the cases. PHBV membrane alone also reduced the severity of adhesions due to its anti-adhesive properties. Histopathological examination revealed limited foreign body reaction due to PHBV. Continuous streptokinase activity in the peritoneal cavity during early post-surgical period prevents postoperative adhesion.

Abdomen↗

PubMed1994

Systemic streptokinase infusion for declotting of hemodialysis arteriovenous fistulas.

In 17 out of 29 hospitalized patients (58.6%) with internal arteriovenous fistula (AVF) thrombosis a systemic streptokinase infusion was used as an alternative to urgent surgical declotting. In the remaining 12 patients (41.4%) fibrinolytic treatment was contraindicated due to the necessity for immediate dialysis, uncontrolled hypertension, active peptic ulcer, known multilevel stenoses of the fistula, or operation 8 days prior to the thrombosis. The systemic streptokinase therapy alone was successful in 9 of 17 patients treated (52.9%), 5 of 17 patients (29.4%) needed the combined therapy (streptokinase plus surgery) and in 3 of 17 patients (17.6%) the fibrinolytic therapy was unsuccessful. No serious complications attributable to the streptokinase infusion were observed. Systemic streptokinase treatment for acute AVF declotting followed by the radiological evaluation of the vessels can be a reasonable alternative to 'blind' surgical emergency reconstruction. The method makes it possible to identify those underlying anatomic abnormalities of the draining vein which may be localized at some distance from the anastomosis and so overlooked during surgery.

Adult↗

PubMed1984

Rethrombosis after reperfusion with streptokinase: importance of geometry of residual lesions.

We tested the hypothesis that lesion rethrombosis after streptokinase reperfusion is related to luminal size of the residual stenosis. Two independent techniques of analyzing coronary angiograms, quantitative coronary angiography and computer-based videodensitometry, were used to estimate the size of the residual lumen immediately after discontinuation of streptokinase. These techniques were selected because they provide independent estimates of cross-sectional area of a lesion with high degrees of reproducibility and minimal observer variability. Twenty-four patients who had undergone successful reperfusion with streptokinase were studied. Seven patients had lesion rethrombosis documented either on a repeat angiogram, at autopsy, or, in one case, by the fact that the patient had an acute transmural infarction resulting in death. Vessel patency was documented by repeat coronary angiography 8 to 14 days after initial streptokinase reperfusion in the other 17 patients. As assessed by quantitative coronary angiography, seven of 13 patients (54%) with minimal luminal cross-sectional areas of less than 0.4 mm2 had rethrombosis. None of the 11 patients with lumens greater than 0.4 mm2 had rethrombosis. In the 17 patients with vessels that remained patent the size of the residual lesion at repeat catheterization was compared with its size immediately after reperfusion with streptokinase. Over the intervening 8 to 14 day interval, an average percentage increase in minimal cross-sectional area of 116 +/- 34% was observed. In seven patients minimal luminal cross-sectional area more than doubled. Integrated optical density, an index of the severity of coronary stenosis derived from computer-based videodensitometry, was also useful in identifying a subgroup of patients at high risk for rethrombosis of lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗

PubMed1984

Global and regional left ventricular function and tomographic radionuclide perfusion: the Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial.

The Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial enrolled 250 patients with acute myocardial infarction. After the coronary angiographic diagnosis of thrombosis, patients were randomly assigned to receive either conventional therapy with heparin or intracoronary streptokinase followed by heparin. Of the 232 patients who survived at least 60 days, 207 (89%) underwent radionuclide ventriculographic determination of global and regional ejection fraction at a single institution at 62 +/- 35 days after infarction. In the first 100 patients, infarct size was also determined by quantitative single-photon emission tomographic imaging with thallium-201 (201Tl) and expressed as a percentage of the left ventricle with a perfusion defect. Overall, global ejection fraction did not differ between patients treated with streptokinase (45.9 +/- 13.9%; n = 115) and control patients (46.1 +/- 14.4%; n = 92, p = NS). Similarly, the regional posterolateral, inferior, and anteroseptal ejection fraction did not differ between the two groups. Infarct size as measured by 201Tl tomography was 19.4 +/- 12.8% (n = 52) of the left ventricle for the streptokinase group and 19.6 +/- 11.8% (n = 48; p = NS) for the control group. When patients were compared within groups by electrocardiographic location of infarction, time to treatment, or the presence or absence of vessel opening, there were no significant differences between streptokinase and control patients. Statistical inclusion of the 18 patients who died early and were unavailable for study also failed to modify the results, except for a possible reduction in inferior infarct size as measured by 201Tl tomography.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Limitation of infarct size and preservation of left ventricular function after primary coronary angioplasty compared with intravenous streptokinase in acute myocardial infarction.

BACKGROUND: Early and effective flow through the infarct-related vessel is probably of paramount importance for limitation of infarct size and preservation of left ventricular function in patients with acute myocardial infarction. Primary coronary angioplasty may offer advantages in these respects compared with thrombolytic therapy. The purpose of the present study was to assess the effects on estimated enzymatic infarct size and left ventricular function in patients with acute myocardial infarction randomly assigned to undergo primary angioplasty or to receive intravenous streptokinase. METHODS AND RESULTS: We evaluated 301 patients with signs of acute myocardial infarction and without contraindications for thrombolysis who presented within 6 hours after onset of symptoms or between 6 and 24 hours if there was evidence of ongoing ischemia. One hundred fifty-two patients were randomly assigned to undergo primary angioplasty, and 149 patients were assigned to receive treatment with streptokinase (1.5 million U i.v.). Infarct size was estimated from enzyme release. Global left ventricular ejection fraction and regional wall motion, if possible in combination with exercise testing, were evaluated by radionuclide ventriculography before discharge. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 through the infarct-related vessel within 120 minutes after admission was achieved in 92% of all patients assigned to receive primary angioplasty therapy. Myocardial infarct size was 23% smaller in the angioplasty group compared with patients assigned to receive streptokinase (1003 +/- 784 versus 1310 +/- 1198 U/L, P = .012). Global left ventricular ejection fraction (50 +/- 9% versus 45 +/- 11%, P < .001) and regional wall motion in the infarct-related zones (42 +/- 14% versus 34 +/- 13%, P < .001) were better in the angioplasty group, which could mainly be contributed to myocardial salvage in the infarct-related areas. The observed differences were more pronounced in patients with an anterior wall myocardial infarction, although patients with a nonanterior infarct location also showed a beneficial effect of primary coronary angioplasty on left ventricular function compared with streptokinase therapy. Furthermore, the observed differences appeared to be more pronounced in patients presenting relatively early (within 2 hours) after onset of symptoms. CONCLUSIONS: In patients with acute myocardial infarction, primary angioplasty results in a smaller infarct size and a better preserved myocardial function compared with patients randomized to receive treatment with intravenous streptokinase. This is probably due to early and optimal blood flow through the infarct-related vessel, as can be accomplished in a very high percentage of patients undergoing primary coronary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed1996

Age and outcome with contemporary thrombolytic therapy. Results from the GUSTO-I trial. Global Utilization of Streptokinase and TPA for Occluded coronary arteries trial.

BACKGROUND: Elderly patients with acute myocardial infarction have much to gain from reperfusion with thrombolytic therapy but are also at increased risk of adverse events. We examined outcomes according to age of patients receiving thrombolysis in an international trial. METHODS AND RESULTS: Patients were randomized to streptokinase plus subcutaneous heparin, streptokinase plus intravenous heparin, accelerated tissue plasminogen activator (TPA) plus intravenous heparin, or streptokinase and TPA plus intravenous heparin. Clinical outcomes at 30 days (death, stroke, and nonfatal, disabling stroke) and 1-year mortality were summarized descriptively for patients aged < 65 (n = 24,708), 65 to 74 (n = 11,201), 75 to 85 (n = 4625), and > 85 years (n = 412) and assessed as continuous functions of age. Older patients had a higher-risk profile with regard to baseline clinical and angiographic characteristics. Mortality at 30 days increased markedly with age (3.0%, 9.5%, 19.6%, and 30.3% in the four groups, respectively), as did stroke, cardiogenic shock, bleeding, and reinfarction. Combined death or disabling stroke occurred less often with accelerated TPA in all but the oldest patients, who showed a weak trend toward a lower incidence with streptokinase plus subcutaneous heparin: odds ratio 1.13; 95% confidence interval 0.6, 2.1. Similarly, accelerated TPA treatment resulted in lower 1-year mortality in all but the oldest patients (47% TPA versus 40.3% streptokinase). CONCLUSIONS: Lower mortality and greater net clinical benefit were seen with accelerated TPA in patients aged < or = 85 years. Because data are limited for patients aged > 85 years, the relative superiority of a given thrombolytic regimen cannot be determined. The interactions of stroke and mortality with newer thrombolytic strategies must be examined explicitly in older patients.

Aged↗

PubMed1993

Comparison of hirudin and heparin as adjuncts to streptokinase thrombolysis in a canine model of coronary thrombosis.

Recombinant desulfatohirudin (HI), a potent and specific thrombin inhibitor, was compared with heparin (HE) as an adjunct to streptokinase thrombolysis. In pentobarbital-anesthetized dogs, an occlusive thrombus (whole blood+thrombin) was introduced into the left anterior descending coronary artery (LAD) with superimposed endothelial damage and distal high-grade stenosis. Intravenous infusion of saline (vehicle), HI (0.3 mg/kg followed by 0.3 mg/kg per hour, 1 mg/kg followed by 1 mg/kg per hour, or 2 mg/kg followed by 2 mg/kg per hour), or HE (60 units/kg followed by 40 units/kg per hour or 100 units/kg followed by 60 units/kg per hour) was initiated 15 minutes before streptokinase (750,000 units for 60 minutes) administration. Vessel patency was monitored for 180 minutes after streptokinase administration with a volume flow probe on the proximal LAD. In dogs treated with no adjunctive agent (saline control), none of the vessels were recanalized with streptokinase. Both HI and HE promoted reperfusion, inhibited reocclusion, and reduced the residual thrombus mass in a dose-dependent fashion. However, at comparable levels of therapeutic anticoagulation (activated partial thromboplastin time [APTT] = 1.5-2.0 times baseline) HI exhibited a higher incidence of reperfusion (eight of eight dogs [100%] versus one of eight dogs [12%]), a shorter time to reperfusion (33 +/- 6 versus 59 minutes), a longer duration of initial reperfusion (106 +/- 21 versus 10 minutes), and a smaller residual thrombus mass than did HE. Likewise, the slope of the relation between the APTT prolongation and the total reperfusion time ("anticoagulation/antithrombosis profile") was almost five times higher for the combined HI data than for the HE data. Our results indicate that HI is more effective than HE in enhancing and sustaining coronary recanalization with streptokinase at a HI dose that modestly prolongs coagulation time and does not alter bleeding times.

Animals↗

PubMed2004

Intrapleural streptokinase for empyema and complicated parapneumonic effusions.

We conducted a single-center, randomized, placebo-controlled trial to determine whether streptokinase instillations adjunctive to chest tube drainage reduce the need for surgery and improve outcome in patients with pleural empyema. Fifty-three patients (frank pus aspirated, 81%; microbiological agent cultured, 62%; mean effusion pH, 6.6 +/- 0.4) received antibiotic treatment, chest tube drainage, and once-daily pleural rinses with either normal saline or normal saline with streptokinase (250,000 IU). Nine patients were excluded for various reasons before pleural rinses were started. Streptokinase (n = 22) was instilled over 4.5 +/- 2 days and saline (n = 22) was instilled over 3 +/- 1.3 days. One patient in each group died during treatment. Clinical treatment success and need for referral to surgery were the main outcome measures. No difference was observed after 3 days. After 7 days, streptokinase-treated patients had a higher clinical success rate (82 vs. 48%, p = 0.01) and fewer referrals for surgery (45 vs. 9%, p = 0.02). No significant radiologic or functional differences were observed between groups during follow-up over 6 months. We conclude that intrapleural streptokinase adjunctive to chest tube drainage reduces the need for surgery and improves the clinical treatment success in patients with pleural empyema.

Adult↗

PubMed1992

Short- and long-term comparative study of anistreplase versus streptokinase in acute myocardial infarction.

Streptokinase is well established as an effective thrombolytic. Anistreplase, a new thrombolytic drug, is a complex of streptokinase and acylated human plasminogen that can be administered by intravenous bolus and activates plasminogen at the clot site. Although both streptokinase and anistreplase are effected in treating myocardial infarction (MI), they have different pharmacologic properties. This study was designed to identify short- and long-term differences in their clinical effectiveness, safety in use, and survival rates in patients with acute MI. One hundred ten successive patients under seventy years of age admitted within three hours after onset of sustained chest pain suggestive of acute MI were randomized to receive either 30 units of anistreplase intravenously over five minutes or intravenous injection of 750,000 units of streptokinase over thirty to sixty minutes. Reperfusion was achieved in 34 of the 52 (65%) patients treated with anistreplase and in 41 of the 58 (71%) patients treated with streptokinase (p = NS). The two drugs were equally effective in preserving left ventricular ejection fraction, which was found to be significantly better in patients with anterior wall MI who had achieved reperfusion than it was in those who did not (p less than 0.02). One-month, twelve-month, and thirty-six-month survival rates were high (96% to 88%) with no significant difference between the two treatment groups. The authors conclude that the two drugs are equally effective thrombolytic agents but that anistreplase has the advantage that it can be administered as a bolus injection.

Aged↗

PubMed1998

North Baden venous lysis trial (NBVL): multicentre prospective randomized phlebographically controlled trial on the effect of ultra-high versus conventional doses of streptokinase in fresh leg-pelvis venous thromboses.

Since no previous randomized comparison has been carried out between ultra-high and conventional dosage streptokinase therapy of fresh venous thromboses, the NBVL trial was carried out as a prospective, randomized, multicentre, phlebographically monitored comparison of the results and adverse effects of these two fibrinolytic treatment options. Using the normal exclusion criteria, 156 patients with a leg-pelvis venous thrombosis presumed to be a maximum of 14 days old were treated with 1.5 million U streptokinase/h for 6h daily (n = 77, group A) or conventional dosage with 100,000 U streptokinase per hour (n = 79, group B). There were 15 patients (eight in group A, seven in group B) who had to stop therapy prematurely, and eight patients (five in group A, three in group B) could not be evaluated because of incorrect monitoring times. The phlebograms were evaluated using IFP-C scores. These showed a reduction in the IFP score from 4.55 to 2.2 in the 64 patients in group A after a mean of 2.7 +/- 0.6 therapy cycles with administration of 24.4 +/- 5.7 million U streptokinase, i.e. 47% of the baseline value. The 69 patients in group B had a reduction in score from 4.2 to 2.93 after a mean of 3.7 +/- 1.2 days of treatment with administration of 8.6 +/- 3.3 million units, i.e. a fall of 30% in the baseline values (p = 0.007). There were 132 out of 281 completely occluded venous segments in group A (47%) and 81 out of 279 segments in group B (29%) that showed complete patency. Eight out of 27 three-segment occlusions in group A and only one of 26 in group B showed complete patency. The IFP score improved by 55% in the 45 men in group A, compared with only 30% in the 47 men in group B (p = 0.002). When both dosages are combined, men showed a greater improvement in IFP score than women (42 versus 29%; p = 0.02). The IFP score improved more in the 20 patients aged more than 60 years in group A than in the 19 patients aged over 60 years of age in group B (61 versus 20%; p = 0.003). No other significant differences in effect were seen on analysis of sub-groups and individual factors (sex, age, presumed age of thrombus and side of thrombosis). In the 77 patients in group A, haemorrhagic complications were less frequent than in the 79 patients in group B (22.1 versus 36.7%; p = 0.054), especially concerning urogenital haemorrhage (6.5 versus 22.8%; p = 0.004). Women were affected more frequently by haemorrhagic complications than men (35.2 versus 26.5%), and the 19 patients aged more than 65 years old were affected more than the 137 younger patients (21.1 versus 13.9%). There were no deaths, and clinically insignificant pulmonary emboli occurred three times. Ultra-high dosage streptokinase shows better and more rapid thrombolytic treatment for popliteal-femoral-iliac venous thromboses and causes fewer haemorrhagic complications than conventional dosage streptokinase. The better effect of ultra-high dosage can be observed particularly for three-segment occlusion as well as in male patients. In older patients, accurate diagnosis is required because of the higher rate of haemorrhagic complications.

Adult↗

PubMed2004

Analysis of five streptokinase formulations using the euglobulin lysis test and the plasminogen activation assay.

Streptokinase, a 47-kDa protein isolated and secreted by most group A, C and G ss-hemolytic streptococci, interacts with and activates human protein plasminogen to form an active complex capable of converting other plasminogen molecules to plasmin. Our objective was to compare five streptokinase formulations commercially available in Brazil in terms of their activity in the in vitro tests of euglobulin clot formation and of the hydrolysis of the plasmin-specific substrate S-2251. Euglobulin lysis time was determined using a 96-well microtiter plate. Initially, human thrombin (10 IU/ml) and streptokinase were placed in individual wells, clot formation was initiated by the addition of plasma euglobulin, and turbidity was measured at 340 nm every 30 s. In the second assay, plasminogen activation was measured using the plasmin-specific substrate S-2251. Streptase was used as the reference formulation because it presented the strongest fibrinolytic activity in the euglobulin lysis test. The Unitinase and Solustrep formulations were the weakest, showing about 50% activity compared to the reference formulation. All streptokinases tested activated plasminogen but significant differences were observed. In terms of total S-2251 activity per vial, Streptase (75.7 +/- 5.0 units) and Streptonase (94.7 +/- 4.6 units) had the highest activity, while Unitinase (31.0 +/- 2.4 units) and Strek (32.9 +/- 3.3 units) had the weakest activity. Solustrep (53.3 +/- 2.7 units) presented intermediate activity. The variations among the different formulations for both euglobulin lysis test and chromogenic substrate hydrolysis correlated with the SDS-PAGE densitometric results for the amount of 47-kDa protein. These data show that the commercially available clinical streptokinase formulations vary significantly in their in vitro activity. Whether these differences have clinical implications needs to be investigated.

Blood Coagulation Tests↗

PubMed1995

How safe is the readministration of streptokinase?

Streptokinase is an antigenic thrombolytic agent used for the treatment of acute myocardial infarction. It reduces mortality as effectively as the nonantigenic alteplase in most infarct patients while having the advantage of being much less expensive. This cost implication is important since myocardial reinfarction is common, with fibrinolytic therapy indicated in many patients with reinfarction. Following streptokinase, antistreptokinase antibodies and neutralisation titres can rise to significant levels from 4 days after the initial dose. These antibodies can presist for at least 4 years in up to 50% of patients. It is possible that these antibodies may cause allergic reactions or neutralisation of a further dose of streptokinase, rendering it ineffective for the treatment of myocardial reinfarction. To date, 2 small studies of patients without previous streptokinase exposure suggest that higher antibody titres are associated with a lower rate of coronary reperfusion, while a further study suggests that high titres are associated with hypersensitivity reactions. At present the readministration of streptokinase cannot be recommended from 4 days after a first dose. Further larger studies are needed to assess the effect of high neutralisation titres on coronary reperfusion.

Animals↗

PubMed1995

Does the potential for development of streptokinase antibodies change the risk-benefit ratio in older patients?

In patients with acute myocardial infarction (MI), quick initiation of thrombolytic therapy is the best strategy for improvement of survival and reduction of morbidity. Streptokinase, a purified product of haemolytic streptococci, is the most commonly administered agent. The compound anistreplase (a complex of streptokinase to plasminogen), is available but currently not often used. The non-antigenic competitor for these two compounds for the indication of MI is alteplase (recombinant tissue plasminogen activator, rt-PA). Due to former use of streptokinase or its derivative anistreplase, patients may develop specific antibodies to the foreign protein, whereas cross-reacting antibodies may be due to streptococcal infections. These antibodies may neutralise streptokinase or its derivative in case of (re)administration and may mediate adverse events, sometimes serious. Since advanced age by itself is certainly not a contraindication to thrombolytic therapy, and because reinfarction occurs frequently, the benefit-risk ratio of re-exposure to streptokinase or its derivative is decreased in the elderly who present with reinfarction. In the framework of tailored thrombolytic therapy, alteplase or urokinase appear to be the drugs of choice in these patients.

Aged↗

PubMed1987

An interim report of the efficacy and safety of anisoylated plasminogen streptokinase activator complex (APSAC).

Anisoylated plasminogen streptokinase activator complex (APSAC) is a thrombolytic agent which can be administered to patients with acute myocardial infarction by intravenous injection rather than prolonged infusion, and which has sustained fibrinolytic activity, inducing thrombolysis with a low risk of early rethrombosis. In clinical trials, APSAC 30U intravenously produced angiographically confirmed reperfusion in 86/156 patients (55%) and coronary patency (in the absence of pretreatment angiography) in 131/161 patients (81%) up to 90 minutes after treatment. These figures compared with a reperfusion rate of 65% (71/110 patients) for intracoronary streptokinase, and a patency rate of 53% (27/51 patients) with intravenous streptokinase. Reperfusion occurred at a mean of about 45 minutes after either APSAC or streptokinase, and APSAC was more effective when administered within 4 hours, than between 4 and 6 hours, after the onset of symptoms of infarction. Reocclusion occurred in 4% (3/80) of infarct-related arteries assessed angiographically 1 to 3 days after APSAC, compared with 10% (7/74) after streptokinase. Preliminary analysis of mortality data from studies involving APSAC suggests a trend towards improved survival with APSAC in comparison with conventional therapy. Among 1855 patients treated with APSAC, and observed for periods of 1 month to 1 year, there have been 115 deaths (6.2%). This compares with a mortality of 12.3% among patients receiving non-thrombolytic therapy (n = 708). The results of large controlled mortality studies are awaited before evaluation of the precise extent of improvement with APSAC can be made. APSAC has been associated with relatively few serious side effects. Analysis of case records for 834 patients who received APSAC 30U intravenously revealed at least 1 suspected side effect in 44%, compared with in 33% of placebo-treated patients (n = 138). Cardiovascular (e.g. arrhythmias and reduction in blood pressure) and haemorrhagic events (mostly associated with puncture sites) were reported most frequently. Cerebrovascular accidents occurred in 15/1598 patients (0.9%) treated with APSAC, of which 10 cases could possibly have been related to treatment. Allergic-type reactions (e.g. anaphylaxis, bronchoconstriction, skin rashes) occurred in 61/1152 patients (5%) after APSAC and may have resulted from previous exposure to streptococcal infection. APSAC induces systemic fibrinogenolysis and a 'lytic' state characterised by reductions in fibrinogen, plasminogen, Factors II, V and VIII and alpha 2-antiplasmin, and an increase in fibrin degradation products, which return to normal over a period of 2 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Anistreplase↗

PubMed1987

Treatment of frostbite with i.v. streptokinase: an experimental study in rabbits.

Experiments were conducted in 32 rabbits to determine whether treatment with IV streptokinase can effectively limit the extent of tissue damage associated with frostbite injury of the hind limbs. Other variables studied were the temperature of the tissue during freezing, the time taken to rewarm the exposed limbs, and the delay between the initiation of treatment with streptokinase and cessation of freezing. A control group of 16 rabbits was not given streptokinase. The extent of tissue damage was estimated by sequential radionuclide perfusion scans of the exposed limbs. This estimate was based on the proportional loss of tissue perfusion on subsequent twice-weekly nuclear scans in comparison with that shown by scans performed immediately after thawing. Pathologic changes in exposed tissues were studied by histology. Streptokinase treatment and rapid rewarming both resulted in less tissue damage at all freezing temperatures. Streptokinase was most beneficial when given 12 hr after freezing, but was effective even when treatment was delayed up to 48 hr.

Animals↗

PubMed1994

Effects of streptokinase and urokinase on microarterial thrombosis and haemostasis. An experimental study in rabbits.

The effects of streptokinase and urokinase on haemostasis, accumulation of platelets radiolabelled with phosphorus (32P) and patency were studied after arteriotomy and deep vessel wall trauma of the central arteries of rabbits' ears. In one study, 12 rabbits were given 1700 IU/kg body weight of streptokinase or urokinase as intraaortic bolus injections five minutes before vascular reperfusion (opening of vascular clamps). A further six were given saline (controls). In the second, 12 further rabbits were each given 3,400 IU/kg of either substance, one fifth as a bolus before reperfusion and the remainder as a continuous infusion during the next two hours. A further six were given saline (controls). Irrespective of the dosage regimens, neither substance improved patency compared with saline-treated controls. Separate dose response studies with streptokinase showed that bolus or bolus+infusion doses larger than those given caused troublesome arteriotomy bleeding. Compared with controls, streptokinase increased, and urokinase decreased, accumulation of platelets. This was not reflected in differences in patency rates, which were similar in all groups. In conclusion, fibrinolytic stimulation with non-thrombolytic doses of streptokinase or urokinase did not prevent microarterial thrombosis in rabbits. The therapeutic index for these substances in clinical microvascular surgery is probably low, as haemorrhagic complications may be expected.

Animals↗