Dose Of Streptokinase Research Articles

Changes in oxidative stress haemostatic parameters during the thrombolytic treatment of pulmonary embolism

Acute pulmonary embolism is the third most common cause of cardiovascular mortality. Thrombolytic treatment of massive pulmonary embolism can be complicated with haemorrhage, re-thrombosis and oxidative stress. The purpose of this study was to evaluate the changes in platelet aggregation, haemostatic, leukocyte function parameters and oxidative stress in patients with acute pulmonary embolism treated with thrombolytics. Fifteen patients undergoing thrombolysis with ultra-high dose streptokinase ( n = 8), or alteplase ( n = 7) treatment were studied. Arterial blood samples were taken before (baseline) and after thrombolysis between the 4th and 24th hour at every four hours, on the second day twice a day and daily on the 3rd, 4th, 5th and 30th day. Platelet aggregation was examined as spontaneous and induced aggregation with adrenaline, collagen and adenosine diphosphate. D-dimer and fibrinogen were measured 8 hourly on the first day and later at the same time intervals as above. To analyse oxidative stress, blood samples were collected prior to thrombolysis, and then 8 hours, 1, 3, 5 and 30 days after treatment. Malondialdehyde, reduced glutathion, plasma sulphydryl groups levels, superoxide dismutase and myeloperoxidase enzyme activities were measured in plasma or whole blood for monitoring of the oxidative stress markers. Production of reactive oxygen species in whole blood was measured by luminol dependent chemiluminescence. Flow cytometry was used to determine CD11a, CD18, and CD97 surface antigen expression on leukocytes. In streptokinase group, adrenaline induced platelet aggregation decreased at the 4th and 8th hour ( p < 0.03) and was significantly lower than in the alteplase group at the 36th hour and on the 3rd day. Platelet aggregation induced by adenosine diphosphate was lower at the 4th hour than at baseline in streptokinase group ( p < 0.05). Collagen induced platelet aggregation was lower at the 4th and 8th hour than at baseline ( p < 0.05) in streptokinase group. Compared to baseline, fibrinogen levels decreased in both groups after thrombolysis. D-dimer levels elevated significantly in both therapeutic groups at the 8th hour. Spontaneous platelet aggregation was not detectable and major bleeding or re-embolism was not documented. The elevated malondialdehyde, reactive oxygen species and myeloperoxidase, decreased reduced glutathion and plasma sulphydryl levels indicated the presence of oxidative stress in patients with pulmonary embolism. Malondialdehyde significantly increased, reduced glutathion significantly decreased following thrombolysis. Reactive oxygen species production peaked on the 3rd and 5th days. Thrombolysis was accompanied by significant decrease in granulocyte and monocyte CD11a and CD18 as well as in granulocyte CD97 expression ( p < 0.05). Massive/submassive pulmonary embolism and thrombolysis injures inducible platelet aggregation. The changes in fibrinogen levels correlate significantly with the improvement of pulmonary perfusion which shows the effect of thrombolysis. Pulmonary embolism induced oxidative stress was detected on patients before thrombolysis. Thrombolytic treatment of pulmonary embolism augmented the increase of oxidative stress response and leukocyte activation following reperfusion, and these parameters normalised only on the 30th day.

Using livers from donation after cardiac death donors—A proposal to protect the true Achilles heel

As the waiting list for organ transplant continues to increase (over 90,000 candidates as of May 30, 2007), the pressure to increase the number of donor organs is the impetus to expand the use of organs from donation after cardiac death (DCD) donors. The focus on DCD, previously referred to as non–heart-beating donor (NHBD), has led to significant increases in its utilization (Table 1), although the contribution to the donor pool remains only 7% in the United States and is disproportionately reflected in increased kidney transplants (Table 2). Prior to the acceptance of brain death, donors were required to have cessation of heart function in order to procure organs for transplantation. In some areas where brain death legislation has not been widely adopted, such as Asia, DCD represents a significant source of organs for transplantation. Although the Maastricht Conference on DCD in 1994 identified 4 categories of DCD [Category I: dead on arrival; Category II: unsuccessful resuscitation; Category III: waiting cardiac death; and Category IV: cardiac death in a braindead donor], it is easier to envision DCD based on two distinct populations, one following uncontrolled cardiopulmonary arrest (Categories I and II) and the other under conditions of controlled removal from life support, without the criteria for brain death being fulfilled. In 1995, the University of Pittsburgh provided one of the earliest comparisons between controlled and uncontrolled DCD. There were 24 DCD livers, 14 in the uncontrolled group (Group 1) and 10 in the group in which controlled termination of life support was performed in the operating room (Group 2). Of the liver grafts that were used, the immediate graft function rate was 50% (3/6) in Group 1 and 100% (6/6) in Group 2; however, the overall 2-year patient and graft survival was only 58% and 33%, respectively. In order to improve outcomes with DCD donors, the decision was made to avoid using uncontrolled DCD livers and, with further experience, to more carefully control risk factors [e.g., avoidance of old ( 60 year old) DCD donors, avoidance of donors with long ( 60 minutes) warm ischemic times during procurement, avoidance of confounding factors in the DCD donors, and minimization of cold ischemic times]. While patient survival and graft survival have improved in more recent eras, the impact of DCD on liver transplantation, as assessed from the Scientific Registry of Transplant Recipients (SRTR) database, shows that DCD graft survival was significantly lower than that of donation after brain death (DBD) grafts, with 1and 3-year graft survival of 70.2% and 63.3% for DCD recipients versus 80.4% and 72.1% for recipients of livers from conventional DBD donors. Recipients of a DCD graft had a greater incidence of primary nonfunction (11.8 versus 6.4%) and retransplantation (13.9% versus 8.3%) compared with DBD recipients. Similar findings have also been reported at single centers 12,13 The mandated period of warm ischemia imposed during the process of certifying death in controlled DCD leads to stagnation of blood in the microcirculation.

Evaluation of oxidative stress in the thrombolysis of pulmonary embolism

To analyse leukocyte function parameters and oxidative stress (OS) in patients with acute pulmonary embolism (PE) treated with thrombolytics. Fifteen patients undergoing thrombolysis (TL) with ultra-high dose streptokinase (n = 8), or alteplase (tPA) (n = 7) treatment were studied. Blood samples were collected prior to TL, and then 8 h, 1, 3, 5 and 30 days after treatment. Malondialdehyde (MDA), reduced glutathione (GSH), plasma protein sulfhydryl groups (PSH) levels, superoxide dismutase (SOD) and myeloperoxidase enzyme (MPO) activities were measured in plasma or whole blood for monitoring of the OS markers. Production of reactive oxygen species (ROS) in whole blood was measured by luminol dependent chemiluminescence. Flow cytometry was used to determine CD11a, CD18, and CD97 surface antigen expression on leukocytes. The elevated MDA, ROS and MPO, decreased GSH and PSH levels indicated the presence of OS in patients with PE. MDA significantly (P < 0.05) increased, GSH significantly (P < 0.05) decreased following thrombolysis. ROS production peaked on the 3rd and 5th days. TL was accompanied by significant decrease in granulocyte and monocyte CD11a and CD18 as well as in granulocyte CD97 expression (P < 0.05). PE led to OS that was augmented following TL. Decreased adhesion molecule expression of circulating leukocytes in the early phase of TL reflects the pathological leukocyte endothelial cell interactions.

Utilidad de la terapia trombolítica con estreptokinasa a dosis baja en infarto agudo del miocardio

The optimal dose of Streptokinase in the treatment of acute myocardial infarction is not well established. Apparently, the thrombolytic efficacy would not increase with doses over 750,000 units. To compare the effectiveness and safety of treatment with low doses of Streptokinase, ranging from 500,000 to 750,000 units, in patients with ST elevation acute myocardial infarction. From September 1993 to September 1998, the GEMI register of patients with acute myocardial infarction, was carried out in 37 hospitals, incorporating 4,938 patients. Of these, 1,631 patients received streptokinase. According to the administered dose of Streptokinase, patients were divided in two groups: 1,465 patients who received 1.5 millions U in 60 minutes (classical therapy group), and 166 patients with ischemic chest discomfort and either ST-segment elevation or left bundle-branch block on the electrocardiogram, who received 500,000 to 750,000 U streptokinase administered in no more than 30 minutes, with heparin, within 0 to 6 hours of symptom onset. Successful reperfusion, mortality, complications, and hospital outcome was evaluated in both groups. The low dose group of patients had a better reperfusion criteria profile. No differences between groups were observed in patient evolution, mortality, maximum Killip classification, post myocardial infarction heart failure, ischemic complications, arrhythmias or mechanical complications. These results suggest that streptokinase in low doses is at least as effective as classical therapy, in the treatment of ST elevation acute myocardial infarction.

Small-vessel thrombosis following vascular injury. Successful treatment with a low-dose intra-arterial infusion of streptokinase.

Abstract Streptokinase may cause excessive haemorrhage if administered systemically in the presence of vascular injury. A patient in this situation was treated with a low dose of streptokinase administered intra-arterially. Using this régime there was little evidence of systemic activation and insignificant bleeding, but there was satisfactory dissolution of the occlusive thrombus.

Effectiveness of Intrapericardial Administration of Streptokinase in Purulent Pericarditis

Purulent pericarditis is very rare. However, among patients suffering from this disease the mortality rate is very high. The aim of this study was to evaluate the effectiveness and side effects of intrapericardial streptokinase administration in patients with confirmed purulent pericarditis. Three patients, one 50-year-old man and two women aged 64 and 40 years, who were admitted to the intensive care unit (ICU) due to purulent pericarditis, entered the study. In all three cases a subxiphoid pericardiotomy followed by insertion of a drainage line into the pericardial space was performed. Antibiotic therapy was started immediately on admission to the hospital. Despite continued antibiotic therapy in all three patients, daily drainage from the pericardium--during several days after surgery--staggered between 50-200 ml/day. Due to considerable purulent pericardial drainage loculations and/or fibrin deposits confirmed by echocardiography, streptokinase (500,000 IU dissolved in 50 ml of normal saline) was administered into the pericardial space over 10 min, using the previously inserted drainage catheter. This regimen was repeated after 12 and 24 h. The total dose of streptokinase was 1,500,000 IU. The clinical effect of intrapericardial streptokinase administration was excellent. Several days after intrapericardial administration of streptokinase, drainage of purulent pericardial fluid stopped. No complications associated with intrapericardial streptokinase administration were observed. In the follow-up echocardiography (in two patients repeated 6 and 9 months after delivery of streptokinase), pericardial fluid and echocardiographic signs of pericardial constriction were not observed. Intrapericardial administration of streptokinase in purulent pericarditis is effective and safe.

Platelet activity and antibody titers after exposure to streptokinase or streptococcal infection

Introduction: Streptokinase use, in acute myocardial infarction, is hindered by failure to reperfuse (60%) and early reocclusion (16%). This phenomenon may, among other causes, be due to systemic inactivation of streptokinase, as well as streptokinase-induced platelet aggregation and clot propagation from antibodies to streptokinase produced after streptokinase administration or streptococcal infections. The purpose of this study was to determine the incidence of streptokinase-induced, antibody-mediated, platelet activation and aggregation after administration of SK or development of a streptococcal infection. Materials and methods: We included 45 normal volunteers (Control group), as well as 45 patients who had received streptokinase (Streptokinase group) and 13 who had suffered a severe streptococcal infection (Streptococcal infection group) within the past 3 years. Extent of streptokinase-induced, antibody-mediated, platelet activation and aggregation, as well as anti-streptokinase antibody and streptokinase resistance titers (lowest streptokinase concentration to cause clot lysis within 10 min) were measured. Results: Whereas streptokinase-induced, antibody-mediated, platelet activation was observed in 49% of streptokinase patients and in only 17% and 15% of streptococcal infection patients and normal volunteers ( p<0.05 Streptokinase vs. Control and Streptokinase vs. Streptococcal infection), streptokinase-induced platelet aggregation was observed in 23% of streptokinase patients and streptococcal infection patients, and in none of the control patients ( p<0.05). Conclusions: Streptokinase-induced, antibody-mediated, platelet activation and aggregation occur in patients with high titers of anti-streptokinase antibody and may play a role in failure of streptokinase therapy. Streptococcal infection patients behave like streptokinase patients in terms of the reactivity of their platelets to subsequent streptokinase dose in vitro.

Anti-streptokinase titers and response to streptokinase treatment in Pakistani patients

In order to investigate whether anti-streptokinase (anti-SK) antibody titers have any effect on response to standard dose (1.5 million units) streptokinase (SK) therapy in patients with acute myocardial infarction, anti-SK titers in plasma were determined in 97 such patients. These patients were classified as ‘responders’ or ‘non-responders’ on the basis of a criteria which involved resolution of chest pain in less than 90 min after the start of thrombolysis, greater than 50% reduction of ST segment elevation in two contiguous leads showing maximum elevations in a 12-lead tracing, reperfusion arrythmias and slope of increase in creatine kinase over a 90-min period after initiation of thrombolysis. Anti-SK antibody levels in plasma were determined in these patients as well as in 50 normal healthy subjects by dissolution of clot method. Mean±S.D. anti-SK levels among responders, non-responders and normal healthy subjects were found to be 0.21±0.12, 0.25±0.22 and 0.21±0.15 million units, respectively. A comparison of these mean values by one-way ANOVA revealed no statistical difference ( P=0.68). However, when compared with the reported values for a Western population, these values were found to be significantly higher ( P<0.03). Whereas, compared to the reported values for an Indian population, these were significantly lower ( P<0.0001). 42% of patients appeared to have responded to SK treatment, while 21% were found to be non-responders. There was no association between response to SK and anti-SK titers in these patients suggesting that the standard dose of SK (1.5 million units) may be quite appropriate for the Pakistani population requiring SK treatment for the first time.

Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial

The combination of fibrinolytic therapy and heparin for acute myocardial infarction fails to achieve reperfusion in 40-70% of patients, and early reocclusion occurs in a substantial number. We did a randomised, open-label trial to compare the thrombin-specific anticoagulant, bivalirudin, with heparin in patients undergoing fibrinolysis with streptokinase for acute myocardial infarction. 17073 patients with acute ST-elevation myocardial infarction were randomly assigned an intravenous bolus and 48-h infusion of either bivalirudin (n=8516) or heparin (n=8557), together with a standard 1.5 million unit dose of streptokinase given directly after the antithrombotic bolus. The primary endpoint was 30-day mortality. Secondary endpoints included reinfarction within 96 h and bleeding. Strokes and reinfarctions were adjudicated by independent committees who were unaware of treatment allocation. Analysis was by intention to treat. By 30 days, 919 patients (10.8%) in the bivalirudin group and 931 (10.9%) in the heparin group had died (odds ratio 0.99 [95% CI 0.90-1.09], p=0.85). The mortality rates adjusted for baseline risk factors were 10.5% for bivalirudin and 10.9% for heparin (0.96 [0.86-1.07], p=0.46). There were significantly fewer reinfarctions within 96 h in the bivalirudin group than in the heparin group (0.70 [0.56-0.87], p=0.001). Severe bleeding occurred in 58 patients (0.7%) in the bivalirudin group versus 40 patients (0.5%) in the heparin group (p=0.07), and intracerebral bleeding occurred in 47 (0.6%) versus 32 (0.4%), respectively (p=0.09). The rates of moderate and mild bleeding were significantly higher in the bivalirudin group than the heparin group (1.32 [1.00-1.74], p=0.05; and 1.47 [1.34-1.62], p<0.0001; respectively). Transfusions were given to 118 patients (1.4%) in the bivalirudin group versus 95 patients (1.1%) in the heparin group (1.25 [0.95-1.64], p=0.11). Bivalirudin did not reduce mortality compared with unfractionated heparin, but did reduce the rate of adjudicated reinfarction within 96 h by 30%. Small absolute increases were seen in mild and moderate bleeding in patients given bivalirudin. Bivalirudin is a new anticoagulant treatment option in patients with acute myocardial infarction treated with streptokinase.

Successful clot lysis using low dose of streptokinase in 22 neonates with aortic thromboses

To determine whether intravenous infusion of low dose of streptokinase was effective in lysing umbilical arterial catheter (UAC)-associated aortic thrombi. A prospective cohort study of 31 consecutive newborn infants with UAC-associated aortic thrombi which were detected by abdominal ultrasonography after removal of UAC. Twenty-two infants were treated with intravenous infusion of low dose (1000 U/h) streptokinase, while nine others were not treated due to various contra-indications. Thrombolysis occurred after a mean interval of 2.2 days (standard deviation (SD) = 1.8) in the treated infants. In the untreated infants, spontaneous thrombolysis occurred significantly later, after a mean interval of 16.9 days (SD = 14.7) (95% confidence intervals of difference between mean intervals - 26.0, - 3.4; P = 0.02). Only one treated infant developed mild bleeding directly attributed to streptokinase therapy. Low dose streptokinase infusion was effective and safe in thrombolysing UAC-associated aortic thrombi.

Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction

Continuing efforts are being made to improve thrombolytic therapy for acute myocardial infarction (AMI). The rate of streptokinase (SK) infusion is commonly limited by the hypotension that is induced. If this could be avoided, an accelerated regimen of SK could be given, analagous to that used for other thrombolytic agents such as alteplase. The mechanism of the SK-induced hypotension is unknown, but there is some evidence that platelet-activating factor (PAF) plays a role. The potent PAF receptor antagonist lexipafant (10 mg) (n=35), or matching placebo (n=36), was administered intravenously over 5 min, in a randomized double-blinded protocol, to consecutive patients about to receive SK for AMI; all but three had inferior MI, because of the preference for strategies other than SK therapy in patients with anterior MI. The rate of infusion of SK was set to give 1.5x10(6) units over 30 min, anticipating significant hypotension. Blood pressure fell sharply over the first 10 min of SK administration. The maximum fall in systolic blood pressure occurred between 8 and 12 min, and averaged 43+/-28 mmHg (mean+/-S.D.) and 40+/-26 mmHg in patients given placebo and lexipafant respectively. Systolic pressure having fallen to <90 mmHg, according to protocol the SK administration rate was reduced in 21 of 36 (58%) of patients given placebo and in 19 of 35 (54%) of patients given lexipafant. The total SK dose was given to all subjects over 40.3+/-17.5 and 40.2+/-13.4 min for the placebo and lexipafant groups respectively. Peak and time integrals of creatine kinase were not different in the two groups. There were no adverse effects attributable to lexipafant. It is concluded that the PAF receptor antagonist lexipafant has no significant effect on SK-induced hypotension and does not facilitate an accelerated regimen of administration.

Streptokinase in acute ischemic stroke: an individual patient data meta-analysis : The Thrombolysis in Acute Stroke Pooling Project.

Three major randomized controlled trials of streptokinase in acute ischemic stroke were curtailed because of safety concerns. The prospective Thrombolysis in Acute Stroke Pooling Project (TAS-PP) was established to examine the aggregate data to identify factors influencing the effect of streptokinase. Individual patient data from the Australian Streptokinase Trial (ASK), Multicentre Acute Stroke Trial-Europe (MAST-E), Multicentre Acute Stroke Trial-Italy (MAST-I), and Glasgow Trial (Glasgow) were pooled. Multivariate modeling determined the interaction between treatment effect and delay from symptom onset to treatment, predicted baseline risk, age, concomitant aspirin or heparin use, and the presence of early CT signs on the outcomes of 10-day death, death and disability, or death alone at 3 or 6 months. Patients' records were pooled (total 1292 patients; streptokinase, n=653, no streptokinase n=639). The subgroup analysis of treatment effect according to delay from symptoms to inclusion shows only a trend toward a better treatment effect with shorter delay, which is not statistically significant for any outcome. Heavier patients in MAST-E may have had a lower (non significant) risk from the fixed dose of 1.5 million units of streptokinase. Concomitant aspirin increased the excess mortality rates in streptokinase-treated patients (17% without aspirin versus 91% with aspirin, P=0.005). The presence of early CT scan signs did not increase the detrimental effect of streptokinase. Few factors influenced the response to streptokinase. However, earlier administration, lower doses of streptokinase, and avoidance of concomitant aspirin should be considered if further streptokinase trials in acute stroke are planned.

A mutant streptokinase lacking the C-terminal 42 amino acids is less immunogenic

Streptokinase (SK) is the most widely used compound for the treatment of myocardial infarction and the least expensive thrombolytic agent, but a drawback to its use is the widespread presence of anti-SK antibodies (Abs). Clinical failure of the activation of the fibrinolytic system by SK has been reported due to the presence of a high titer of anti-SK neutralizing Abs. Patients receiving SK therapy develop high anti-SK antibody titers, which might provoke severe allergic reactions. These Abs are sufficient to neutralize a standard dose of SK up to four years after initial SK administration. This is a clinical problem because of the increasing number of patients who have been treated once with SK for acute myocardial infarction (AMI) and are likely to require plasminogen activator treatment in the future. In previous in vitro studies, we have shown that a deletion mutant (mut-C42), lacking the 42 C-terminal residues, was significantly less antigenic when compared with the native molecule (SKC-2). In this study, 14 monkeys were subjected to treatment with SKC-2 and mut-C42 in order to compare their humoral response by determining SK neutralizing activity in monkey’s sera. All monkeys developed anti-SKC-2 Ab titers, but in the case where treatment induced Abs directed against the C-terminus of SKC-2, neutralizing activity against the native protein was significantly higher than that developed against mutant SK mut-C42.

IIb/IIIa Receptor blockade in acute myocardial infarction

To appreciate the clinical potential of antiplatelet therapy in the treatment of patients with acute myocardial infarction (MI), it is important to understand the mechanism and pathophysiology of acute MI and to understand the role that platelets play in the process of acute thrombus formation. Recognition of the limitations of current therapy has sparked intense interest in the development of more potent platelet inhibitors such as antagonists of the platelet glycoprotein (GP) IIb/IIIa receptor. Because this receptor represents the final common pathway of platelet aggregation, it emerges as a very attractive therapeutic target for phamacologic interventions. The purpose of this review is to summarize the results of recent large-scale clinical trials that use GP IIb/IIIa antagonist therapy in patients with acute MI both as an adjunct to percutaneous coronary interventions and as an adjunct to exogenously administered fibrinolytic therapy. As an adjunct to percutaneous coronary interventions, GP IIb/IIIa antagonists have shown significant benefit in the prevention of composite end points of death, MI, and emergency revascularization. As an adjunct to fibrinolytic agents, GP IIb/IIIa antagonists enhance the speed and degree of reperfusion achievable pharmacologically. Although the potential risk of bleeding remains a concern (particularly with higher doses of streptokinase), recent phase II trials such as TIMI 14 and SPEED suggest considerable potential for these potent antiplatelet agents in the medical treatment of patients with acute MI. (Am Heart J 1999;138:S164-S170.)

Streptokinase antibodies inhibit reperfusion during thrombolytic therapy with streptokinase in acute myocardial infarction.

To evaluate the influence of pretreatment IgG against streptokinase on the outcome of streptokinase treatment in acute myocardial infarction. Coronary care unit. From 88 patients admitted to the coronary care unit due to chest pain, blood samples were taken for determination of the pre-existing titre of antibodies against streptokinase. The patients were treated and monitored according to standard protocols. Fifty of the patients received thrombolytic therapy with streptokinase due to acute myocardial infarction and were monitored with continuous dynamic vectorcardiography, making possible the continuous analysis of ST- and QRS-vector changes and determination of the event of reperfusion. None of these 50 patients had been given streptokinase therapy previously. According to the vectorcardiographic criteria 21(42%) patients had signs of early (within 2 h) reperfusion after streptokinase therapy. These patients had lower pre-existing antibody titres than patients without signs of reperfusion (mean values 0.20 and 0.45 arbitrary units, P = 0.01). None of the patients with a titre higher than 0.50 arbitrary units (nine patients) had signs of early reperfusion. Of the 41 patients with a titre lower than 0.50 arbitrary units 52.5% had signs of early reperfusion. The present investigation indicates that pre-existing streptokinase antibodies play an important role in reperfusion failure during thrombolytic therapy with streptokinase in acute myocardial infarction. Therefore, the determination of streptokinase antibodies may differentiate between those patients who may benefit from streptokinase treatment and those who should be treated with some other regime.

Ultrasound enhanced thrombolysis in experimental retinal vein occlusion in the rabbit

AIMSTo investigate if it was possible to lower the dose of streptokinase and maintain an effective thrombolysis by adding pulsed low energy ultrasound.Methods—53 retinal veins in 27 rabbits were occluded...

Serum antibody titers in a systemic lytic therapy with streptokinase.

Anaphylactic reactions to streptokinase are rare but potentially life-threatening complications. Gamma E immunoglobulin (IgE) mediated mechanisms, probably due to streptococcal infections, have been implicated. We investigated the value of in vitro laboratory or dermatologic tests in predicting anaphylactic reactions due to streptokinase and the value of antistreptolysin titers (ASL) in predicting the amount of specific IgE (sIgE) and specific gamma G immunoglobulin (sIgG) neutralizing antibodies to streptokinase. We measured serum levels of total IgE, streptokinase sIgE and sIgG, and ASL in 16 patients before and 9 and 41 days after streptokinase therapy. Immediately before therapy, intracutaneous testing with 100 IU streptokinase was done. Dermatologic testing did not identify patients prone to allergic reactions. Moreover, not all patients with increased sIgE levels had allergic reactions. These reactions were independent of the dose of streptokinase given. In spite of steroid prophylaxis, allergic reactions occurred in 3 of 16 patients, but none showed life-threatening anaphylaxis. Streptokinase sIgE and sIgG concentrations were closely related to ASL titers. Plasma levels of sIgG, sIgE, and ASL titers showed a good correlation. We believe ASL titers can be used for the estimation of neutralizing antibodies instead of streptokinase sIgG antibodies. Currently, no laboratory or dermatologic test allows reliable predictions of allergic reactions to streptokinase.

Similar, more than 6-months persisted, antibody and neutralizing activity responses in patients with acute myocardial infarction treated with recombinant or natural streptokinase

Summary One of the main problems in implementing thrombolytic treatment with streptokinase (SK) in cases of acute myocardial infarction (AMI) is its antigenicity. This aspect was prospectively studied in 224 patients with AMI, who were randomly distributed in two groups to receive 1.5 × 106 IU of recombinant (rSK) or natural streptokinase (nSK) less than 12 h after the onset of symptoms. Serum samples were taken before and 10, 90, 180 and 360 days after SK infusion and blindly processed for anti-SK IgG determinations and for anti-SK neutralizing activity. The anti-nSK or anti-rSK circulating IgG antibody level was measured by an enzyme immunoassay (EIA). The neutralizing activity was determined by the inhibition of SK-induced plasminogen activation using a chromogenic substrate hydrolysis assay. The validation of the EIA is described. The profile and magnitude of the anti-SK-IgG response of patients that received nSK were similar to those in patients who received rSK, looking like a typical secondary immune response. These data contribute to their bioequivalency. Six months after SK infusion the anti-SK neutralizing activity was still in the same range as the SK concentration expected after an infusion, suggesting large patient-to-patient variability for the efficacy of a second SK administration in case of re-infarction. At 1 year after SK infusion the antibody concentration and anti-SK neutralizing activity were low in most patients tested, suggesting that a second SK dose will not be inactivated. This does not preclude the appearance of immune complex-dependent reactions, which can occur even if the SK is not inactivated by the antibodies. This aspect should be kept in mind when re-administering SK.

Intrapleural Fibrinolytic Treatment of Traumatic Clotted Hemothorax

To evaluate the role of intrapleural fibrinolytic treatment (IPFT) in traumatic clotted hemothorax. Between August 1995 and February 1997, 24 patients with traumatic clotted hemothorax were included. Streptokinase (SK), 250,000 IU, or urokinase (UK), 100,000 IU, diluted in 100 mL of saline solution was given daily. We administered 5.0+/-1.8 (range, 2 to 9) doses of SK or 6.25+/-5.97 (range, 2 to 15) doses of UK. Dicle University School of Medicine, Thoracic and Cardiovascular Surgery Department. Complete response, which was defined as resolution of symptoms with complete drainage of fluid and no residual space radiographically, occurred in 15 (62.5%) patients. Partial response, which was defined as resolution of symptoms with a small pleural cavity, occurred in seven (29.2%) patients. Two patients (8.3%) required decortication; they were defined as nonresponders. The mean period of time between the diagnosis and fibrinolytic treatment (FT) was 11.65+/-6.38 (range, 4 to 25) days. There were no complications related to IPFT. There was no mortality during the course of IPFT. The use of intrapleural fibrinolytic agents has resulted in resolution of clotted hemothorax with an overall success rate of 91.7%. We recommend that IPFT should be added to the algorithm for management of clotted hemothorax before proceeding with minithoracotomy or pleural decortication.

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

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