High-dose Streptokinase Research Articles

The effects of streptokinase in a Chacma baboon (Papio ursinus) model of acquired thrombotic thrombocytopenic purpura

TTP is a life-threatening disorder with limited pharmaceutical treatment options. Recently, the potential of streptokinase in the treatment of acquired TTP was demonstrated in humans in vitro, and in vivo in a mouse model. We aimed to determine the in vitro and in vivo effects of streptokinase in an established Papio ursinus model of acquired TTP. In vitro: VWF activities & multimer patterns and thromboelastograms were assessed with increasing concentrations of streptokinase. In vivo: After induction of TTP, escalating streptokinase doses (ranging from 50,000 to 900,000IU) were administered, and the effects of streptokinase assessed on peripheral blood counts, fibrinolysis, VWF activities & multimer patterns and thromboelastograms. In an extension of the study, high-dose streptokinase (1,500,000-3,000,000IU) was administered to another baboon. After spiking, fibrinolysis with loss of large VWF multimers was observed at [2200IU/mL]-roughly equivalent to 1,500,000IU. However, administration of escalating intravenous streptokinase doses had no in vivo effect on the TTP phenotype, and in vivo increases in plasmin activity were mild when compared with baseline, even at high doses. Minimal effect on VWF multimer patterns was observed but only at doses ≥ 1500,000IU. Streptokinase is not effective in resolving TTP in a Papio ursinus model of TTP, possibly due to limited activation of the baboon fibrinolytic system. Modifications to this model, the use of alternative higher animal models, or alternative thrombolytics, should be considered to establish proof-of-concept.

Efficacy and safety of high dose versus low dose streptokinase for treatment of submassive pulmonary embolism

Abstract Pulmonary embolism (PE) remains a major cause of morbidity and mortality in the general population, the established treatment for PE is anticoagulation. It has previously been demonstrated that thrombolytic therapy can be lifesaving in patients with massive PE (haemodynamic instability and right heart failure). However, the use of thrombolytic therapy in patients with submassive PE (haemodynamically stable) remains a controversial topic. Recent clinical studies, however, support evidence that thrombolysis may favorably affect the outcomes in a wider spectrum of high risk PE patients presenting with right ventricular dysfunction (RVD) as evidenced by decreased right ventricular end diastolic diameter (RVEDD), disappearance of paradoxical septal motion (PSM), and tricuspid regurge (TR) as well as decrease in the pulmonary artery pressure. The aim of this study was to evaluate the efficacy and safety of high dose streptokinase (SK) in 1 h versus low dose SK in 24 h in patients with submassive PE and RVD (high risk PE). The study included 60 patients (28 males and 32 females, mean age 45.5 ± 13.6 years) with submassive PE (positive spiral CT chest) and RVD (proved by echocardiography). Those without contraindications to SK were randomly assigned to receive either high dose (group I) or low dose (group II) of SK. Those with contraindication(s) to SK received anticoagulation (group III). Echocardiography was done before and 72 h after treatment. Right ventricular dysfunction (RVEDD, PSM, and TR) and mean pulmonary artery pressure (PAP) improved significantly 72 h after treatment in groups I and II, while a slight improvement in PAP was observed after treatment in group III. No significant difference was noticed between groups I and II regarding the effect of treatment on RVD or PAP. Statistically nonsignificant difference was found between groups I and II regarding the complications of SK, however a slightly higher risk of bleeding was observed in group I (high dose SK). No significant difference was found between the three groups regarding the mortality. These data suggest that SK can rapidly and safely reverse the pulmonary hypertension and RVD in contrast to anticoagulation. Both protocols of SK are equieffective in rapid reversal of RVD and pulmonary hypertension. Both protocols were safe as proved by absence of difference in mortality over anticoagulant group.

Hazards of thrombolytic therapy in deep vein thrombosis.

From 1965 to 1985, 64 deep vein thrombosis (DVT) patients were treated with streptokinase (SK). In 26 cases 'high-dose SK' (IV 100,000 units/h for 4 days) was used and in 38 patients a 'low-dose SK' regime (IV 250,000 units every 12 h for 4 days) was employed. The clinical signs of DVT subsided in 78 per cent of treated patients within 30 days of completing SK treatment. A repeat phlebography was performed immediately after SK therapy in 29 patients (45 per cent) and a total recanalization or partial thrombolysis was achieved in 80 per cent of the studied cases. In 15 patients minor and major haemorrhagic complications occurred. There were five fatalities, all in the high-dose SK group (three intracranial haemorrhages and two major bleeds). Three patients developed pulmonary embolism and none of them died. The post-treatment clinical and phlebographic evaluation did not reveal any significant difference between the two methods of SK administration, but more haemorrhagic complications (P less than 0.02, chi=5.50825) occurred in the high-dose SK patients. This report emphasizes the risk of bleeding complications during thrombolytic therapy. If SK is to be used, therefore, careful selection of patients and meticulous monitoring are mandatory.

High-dose streptokinase in the treatment of acute massive pulmonary embolism complicated with cardiogenic shock, respiratory arrest and ventricular fibrillation

Despite advances in prophylaxis, diagnostic modalities, and therapeutic options, pulmonary embolism remains a commonly undiagnosed entity with lethal outcome. Clinically, pulmonary embolism ranges from massive thromboembolism with cardiogenic shock to asymptomatic, microebolism with anatomically small emboli without hemodynamic, respiratory or other disturbances. A patient with massive pulmonary embolism complicated with ventricular fibrillation, respiratory arrest and cardiogenic shock was treated with a total dose of 3 750 000 IU of intravenous streptokinase in the 8-hour time period. After successful cardiopulmonary resuscitation, and thrombolytic therapy, the patient regained hemodynamic stability six hours after admission; all clinical and electrocardiographic signs of the right ventricle insufficiency disappeared. This case report suggested that treatment with the high-dose of streptokinase could be beneficial in the patients with massive pulmonary embolism complicated with cardiogenic shock, which must be confirmed by further randomized trials.

High-dose streptokinase therapy for prosthetic valve thrombosis within 2 weeks of open heart surgery

High-dose streptokinase therapy for prosthetic valve thrombosis within 2 weeks of open heart surgery

Thrombolysis in Central Splanchnic Thrombosis

We present 4 patients treated with streptokinase for different forms of abdominal venous thrombosis. Two patients suffered from central splanchnic venous thrombosis (superior mesenteric vein and bilateral iliac veins in Patient A, portal and superior mesenteric veins in Patient B). Both patients' presenting complaint was abdominal pain. In both, a temporary infection-associated circulating lupus anticoagulant presumably caused this condition. Two other patients presented with isolated portal vein thrombosis without lupus anticoagulant. Thrombolysis with high dose streptokinase (9 MU over 6 hours) successfully reopened the veins involved in all 4 patients. A literature survey showed that thrombolysis is a therapeutic option for mesenteric vein thrombosis, but there was no consensus on which thrombolytic drug should be given or on method of administration.

High-Dose Streptokinase Therapy With Three Million Units in One Hour Significantly Improves Early Coronary Patency Rates in Acute Myocardial Infarction

High-Dose Streptokinase Therapy With Three Million Units in One Hour Significantly Improves Early Coronary Patency Rates in Acute Myocardial Infarction

High-dose streptokinase therapy with three million units in one hour significantly improves early coronary patency rates in acute myocardial infarction

In summary, 60 minutes after beginning fibrinolytic therapy for acute myocardial infarction, significantly higher patency rates were observed after administration of 3.0 million U streptokinase as compared with 1.5 million U in a prospective, randomized, open trial (TIMI grade 2 and 3 in 52% vs 26%; p = 0.04). Thus, twice the conventional dose of streptokinase administered over 1 hour significantly improves very early coronary patency rates and should be studied further.

High Dose Streptokinase + Angioplasty Leads to Reperfusion After MI

High Dose Streptokinase + Angioplasty Leads to Reperfusion After MI

The Therapy of Acute Myocardial Infarction: Current State of the Art

For decades management of acute myocardial infarction (AMI) consisted of bed rest, oxygen, prevention for thromboembolic complications, and treatment of arrhythmias and heart failure. In the last years a more aggressive treatment of AMI has been developed, based on the following three basic principles: (1) Mortality of patients with AMI is determined by the infarct size and the degree of left ventricular dysfunction. (2) The time interval between the onset of coronary occlusion and any intervention to limit infarct size is brief and takes usually not more than three to four hours. (3) After the acute phase of infarction a lot of patients remain at high risk of fatal coronary events, i.e. reinfarctions. The angiographic findings during the first hours of AMI showed in about 80% of patients an obstructive coronary thrombus and led to efforts to dissolve the offending thrombi. The demonstration that coronary thrombi can be lysed in about 80% of cases within 60 minutes after the intracoronary injection of thrombolytic agents (streptokinase or urokinase) has boosted the reperfusion therapy in AMI in the hope that ischemic myocardium might be salvaged. Intracoronary infusion of thrombolytic agents however, can be applied only in a minority of patients with AMI because coronary angiography and a skilled team of investigators are required, therefore a short-time intravenous high dose streptokinase infusion was developed. In the meantime two large double blind randomized trials (ISAM and GISSI) could demonstrate a reduction in hospital mortality in AMI especially by early treatment with intravenous streptokinase. Conventional thrombolytic agents produce a systemic lytic state with the possibility of hemorrhage, therefore recombinant tissuetype plasminogen activator (rt-PA) and two other drugs, acylated streptokinase and pro-urokinase, were developed with the aim of inducing coronary thrombolysis without severe systemic lytic state, but the efficacy of these new drugs remains to be demonstrated in randomized trials versus conventional thrombolytic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of early high-dose streptokinase intravenously on left ventricular function in acute myocardial infarction

One hundred seven patients who recently had acute myocardial infarction were randomly assigned either to standard heparin therapy or to intravenous streptokinase within 5 hours after the onset of symptoms in 7 hospitals without catheterization facilities. In the third week, the patients were referred to a university hospital, where the patency rate of the infarctrelated artery was studied by selective coronary arteriography and left ventricular function by radionuclide angiography. Fifty-five patients received heparin and 52 streptokinase within a mean period of 190 minutes after the onset of symptoms. Seven patients in the heparin group and 4 in the streptokinase group died in hospital. The patency rate of the infarct-related artery was identical in both groups (69% in the heparin group vs 68% in the streptokinase group). Left ventricular ejection fraction was not statistically different (0.44 ± 0.13 in the heparin group vs 0.45 ± 0.12 in the streptokinase group). Left ventricular ejection fraction was significantly higher in patients with a patent infarct-related artery than in patients with an obstructed infarct-related artery (0.49 ± 0.12 vs 0.41 ± 0.15, p < 0.01). In patients with inferior wall infarction, left ventricular ejection fraction was identical (0.50 ± 0.10 in the heparin group vs 0.52 ± 0.09, in the streptokinase group). In patients with anterior wall infarction, left ventricular ejection fraction was significantly higher in the streptokinase group than in heparin group (0.40 ± 0.10 vs 0.33 ± 0.09, p < 0.05). Analysis of regional wall motion revealed that improvement occurred in the lateral wall of the left ventricle. After a mean follow-up of 23 months, 3 patients in the heparin group and 1 patient in the streptokinase group died, yielding the mortality rate at the end of the follow-up period to 18.1 % in the heparin group on 9.6% in the streptokinase group. Thus, early intravenous administration of streptokinase may lead to significant preservation of left ventricular function in patients with anterior wall infarction. One may question the suitability and utility of intravenous thrombolysis in inferior wall infarction.

High dose intravenous streptokinase in acute myocardial infarction--short and long term prognosis.

Streptokinase (1 million international units) was given intravenously over 30 or 60 minutes to 50 patients four hours or less after the onset of acute myocardial infarction. All were aged less than or equal to 70 years and had 4 mm or greater ST segment elevation in anterior or inferior leads. Rapid (mean 95 min) ST segment resolution, which was taken to indicate reperfusion of the myocardium, occurred in 36 (72%) patients. In these 36 the average time from onset of symptoms to peak creatine kinase, creatine kinase MB, and myoglobin was 9.45 hours, whereas it was 17 hours in the 14 patients in whom indirect criteria did not indicate reperfusion. Reperfusion arrhythmias were invariably present and ventricular tachycardia developed in five patients and ventricular fibrillation in two. The infarct related artery was seen to be open in 28 (70%) of the 40 patients who had delayed coronary arteriography. The frequency of patency in the infarct related artery was no different in patients given streptokinase less than 2 hours or between 2-4 hours from onset of symptoms nor did it differ when streptokinase was infused over 30 or 60 minutes. Mean left ventricular ejection fraction was 57% in those with a patient infarct related artery and 48% in those with an occluded vessel. Eight patients subsequently underwent elective percutaneous transluminal coronary angioplasty after successful thrombolysis and six had coronary artery bypass grafting. There were nine in-hospital reocclusions of the infarct related coronary arteries. Two bleeding episodes occurred; one required transfusion. Five of the 50 patients died in hospital. All of them had had an anterior myocardial infarction; four had bifascicular block and one had right bundle branch block. During follow up, four patients died, two suddenly and two from reinfarction. During follow up (mean 15 months) the frequency of reinfarction, dyspnoea, and angina was low and there was no difference in the proportions of patients returning to work between those with an open infarct related artery and those with a closed infarct related artery. Intravenous administration of high dose streptokinase to selected patients during the acute phase of myocardial infarction is a safe, effective, and practical method of thrombolysis. It must, however, be followed by coronary arteriography to select those patients in whom percutaneous transluminal coronary angioplasty or coronary artery bypass grafting will be helpful.

The hypotensive effect of intravenous streptokinase in patients with acute myocardial infarction.

We studied the hypotensive effect of a rapid intravenous infusion of high-dose streptokinase in 98 patients with an acute myocardial infarction. The systolic blood pressure fell from 132 +/- 20 (range 90 to 174) to 97 +/- 21 mm Hg (range 58 to 152) at 15 +/- 8 min (range 4 to 40) after the commencement of the streptokinase infusion (p less than .001). A fall in diastolic blood pressure from 80 +/- 16 (range 51 to 105) to 61 +/- 15 mm Hg (range 32 to 92) accompanied the fall in systolic pressure (p less than .001). The fall in blood pressure was associated with an increase in heart rate (73 +/- 14 to 78 +/- 17 beats/min, p less than .001), preceded the appearance of clinical signs of reperfusion by 37 +/- 38 min and was similar in magnitude and timing in patients with anterior and inferior infarction. There were direct relationships between the rate of infusion of streptokinase and both the magnitude (r = .49, p less than .001) and the rate of fall of systolic blood pressure (r = .67, p less than .001) as well as both the magnitude and rate of fall of diastolic blood pressure. In most patients, the fall in blood pressure was transient (9 +/- 6 min, range = 2 to 30) and easily managed by slowing or stopping the infusion, placing the patient in the Trendelenburg position, or by administering an infusion of low-dose norepinephrine or dopamine. However, in four patients with severe left ventricular dysfunction, severe hypotension persisted for more than 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

STUDIES ON THE MEDICAL TREATMENT OF DEEP VEIN THROMBOSIS

The aim of these studies was to investigate different regimens of thrombolytic therapy and oral anticoagulation, and to evaluate the effects of streptokinase (SK), heparin and warfarin in the treatment of deep vein thrombosis (DVT). Low-dose SK, although controlled according to the fibrinogen levels, did not provide improved thrombolysis compared to conventional high-dose SK, and more postthrombotic changes were registered after an average of 3 years. Furthermore, serious hemorrhagic side-effects occurred, which makes this regimen inexpedient. Various regimens of local venous infusion of SK were tried, and with a dose of 4,000 IU/h for 72 h in combination with heparin a thrombolytic effect was achieved, albeit not greater than usually observed with conventional SK. Systemic hypofibrinogenemia and hemorrhage were not avoided. A hitherto not described side-effect with bullous dermatitis was reported. Venographic severity of calf vein thrombosis displayed a statistically significant correlation to long-term hemodynamic changes, as assessed with foot volumetry, after an average of 5 years. This correlation was stronger for the size of the thrombus after initial treatment than for the size at diagnosis. Thus it seems important to treat calf vein thrombosis with heparin in order to limit the extent of the thrombus, thereby reducing long-term sequelae. During heparin treatment, an average reduction of the thrombi of 17% was observed. This reduction was significantly correlated to a short duration of symptoms but not to parameters of heparin therapy or fibrinolytic components. However, patients with substantial thrombolysis had high plasmin-alpha 2-antiplasmin (PAP) levels, and those with high tissue plasminogen activator (t-PA) inhibitor levels and remarkably also those with high t-PA antigen levels had no lysis. The concentration of t-PA antigen showed a significant increase during heparin infusion, whereas that of PAP and t-PA inhibitor was not influenced. By applying more intensive initial oral anticoagulation, stable therapeutic prothrombin time (PT)-levels were achieved one day earlier and the duration of heparin infusion could be equally reduced compared to the conventional regimen (4.4-5 days vs 5.4-6 days). The activity of coagulation factors II, VII, IX and X had dropped to the same level with both regimens the day heparin was discontinued, observed. The effectiveness of oral anticoagulation after DVT was studied in 596 patients treated for a total of 4450 months.(ABSTRACT TRUNCATED AT 400 WORDS)

A Comparative Randomized Trial of Low-Dose Versus High-Dose Streptokinase in Deep Vein Thrombosis of the Thigh

Fibrinolytic treatment of acute deep vein thrombosis (DVT) of the leg with high-dose streptokinase (SK) (100,000 U/h) in 39 cases, or low-dose SK (approx 10,000 U/h) in combination with low-dose heparin in 41 cases, was studied in a prospective randomized trial. The degree of thrombolysis was similar in both groups and did not correlate with age or size of the thrombus or with fibrinogen level. The degree of late recanalization was also similar in both groups. There were however significantly more patients with postthrombotic changes in the low-dose group than in the high-dose group after a mean follow-up time of 31 and 38 months respectively. In the low-dose group 2 intracranial hemorrhages occurred (one was fatal) and one patient died of pulmonary embolism, but there were significantly less allergic side effects to SK. There were no cases of such serious side effects in the highdose group. Although low-dose SK has equal thrombolytic effect it seems inferior to high-dose SK, since it probably causes more severe hemorrhagic side-effects.

High-dose, brief intravenous streptokinase early in acute myocardial infarction

An acute thrombus at the proximal border of a high-grade atherosclerotic obstruction is the usual cause of myocardial infarction. Although intracoronary thrombolysis is potentially an exciting new therapy for reducing the extent of myocardial infarction by lysing coronary clot, a number of major difficulties limit its widespread application. It is a complex procedure requiring intracoronary visualization and infusion within a few hours of onset of symptoms. Since intravenous streptokinase could be widely applied if effective, we and others have wondered whether high-dose, brief-duration intravenous streptokinase infusion given early in myocardial infarction would lyse coronary clots without bleeding. To date we have treated 13 patients within 6 hours of onset of symptoms and with ECG and angiographic evidence of typical myocardial infarction caused by coronary clot. Clot lysis and angiographically proved coronary reperfusion were achieved in 6 patients within 1 hour of starting a systemic intravenous infusion of 850,000 IU of streptokinase. Schroeder et al., 21 in Berlin, West Germany, achieved angiographically proved coronary reperfusion in 11 of 21 patients with acute myocardial infarction following a 30-minute intravenous streptokinase infusion of 500,000 IU. Neuhaus et al., 22 in Göttingen, West Germany, achieved angiographically proved coronary reperfusion in 24 of 39 similar patients within 48 minutes by intravenous infusion of 1,700,000 IU of streptokinase. In these three studies, no serious bleeding occurred; left ventricular function was improved in patients who achieved coronary reperfusion. We conclude that rapid intracoronary clot lysis and coronary reperfusion can be achieved early in myocardial infarction by brief-duration systemic intravenous infusion of high-dose streptokinase without a high incidence of serious bleeding.