Streptase®, Streptokinase, is a sterile, purified preparation of a bacterial protein elaborated by group C beta -hemolytic streptococci. It is supplied as a lyophilized white powder containing 25 mg cross-linked gelatin polypeptides, 25 mg sodium L-glutamate, sodium hydroxide to adjust pH, and 100 mg Albumin (Human) per vial or infusion bottle as stabilizers. The preparation contains no preservatives and is intended for intravenous and intracoronary administration.

Streptase, Streptokinase, acts with plasminogen to produce an "activator complex" that converts plasminogen to the proteolytic enzyme plasmin. The t ½ of the activator complex is about 23 minutes; the complex is inactivated, in part, by antistreptococcal antibodies. The mechanism by which dissociated streptokinase is eliminated is clearance by sites in the liver; however, no metabolites of streptokinase have been identified. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. Plasmin is inactivated by circulating inhibitors, such as (alpha)-2-plasmin inhibitor or (alpha)-2-macroglobulin. These inhibitors are rapidly consumed at high doses of streptokinase.

Intravenous infusion of Streptokinase is followed by increased fibrinolytic activity, which decreases plasma fibrinogen levels for 24 to 36 hours. The decrease in plasma fibrinogen is associated with decreases in plasma and blood viscosity and red blood cell aggregation. The hyperfibrinolytic effect disappears within a few hours after discontinuation, but a prolonged thrombin time may persist for up to 24 hours due to the decrease in plasma levels of fibrinogen and an increase in the amount of circulating fibrin(ogen) degradation products (FDP). Depending upon the dosage and duration of infusion of Streptokinase, the thrombin time will decrease to less than two times the normal control value within 4 hours, and return to normal by 24 hours.

Intravenous administration has been shown to reduce blood pressure and total peripheral resistance with a corresponding reduction in cardiac afterload. These expected responses were not studied with the intracoronary administration of Streptase, Streptokinase. The quantitative benefit has not been evaluated.

Variable amounts of circulating antistreptokinase antibody are present in individuals as a result of recent streptococcal infections. The recommended dosage schedule usually obviates the need for antibody titration.

Two very large, randomized, placebo-controlled studies (1,2) involving almost 30,000 patients have demonstrated that a 60-minute intravenous infusion of 1,500,000 IU of Streptokinase significantly reduces mortality following a myocardial infarction. One of these studies also evaluated concomitant oral administration of low dose aspirin (160 mg/d over one month).

In the GISSI study the reduction in mortality was time dependent. There was a 47% reduction in mortality among patients treated within one hour of the onset of chest pain, a 23% reduction among patients treated within three hours, and a 17% reduction among patients treated between three and six hours. There was also a reduction in mortality in patients treated between six and twelve hours from the onset of symptoms, but the reduction was not statistically significant.

In the ISIS-2 study the reduction in mortality was also time dependent. If Streptokinase and aspirin were administered within the first hour after symptom onset, the reduction in mortality was 44%. The reduction in the odds of death in patients treated within four hours was 53% for the combination of Streptokinase and aspirin, and 35% for Streptokinase alone. However, the reduction was still significant when treatment was started 5-24 hours after symptom onset: 33% for the combined therapy and 17% for Streptokinase alone. Overall, in the 0-24 hour time period there was a 42% reduction in the odds of death with combined treatment (Streptokinase and aspirin) versus placebo (2p<0.00001) and a 25% reduction in the odds of death with Streptokinase alone versus placebo (2p<0.00001).

One of eight smaller studies using a similar dosing schedule showed a statistically significant reduction in mortality. When all of these studies were pooled, the overall decrease in mortality was approximately 23%. Results from pooling several studies using different dosages with long term infusion corroborate these observations.

In addition, studies measuring left ventricular ejection fraction (LVEF) at discharge showed the mean LVEFs were 3-6 percentage points higher in the Streptokinase group than in the control group. This difference was statistically significant in some of the studies (3,4) . Furthermore, some studies reported greater improvement in LVEF among patients treated within three hours than in patients treated later.

Results from a randomized controlled trial in over 11,000 patients show that, following treatment with IV Streptokinase, there is a reduction in the number of patients with clinical congestive heart failure during the 14-21 day in-hospital period. Clinical congestive heart failure occurred in 12.8% of Streptokinase-treated patients compared with 15% of the control patients (p=0.001) (1) .

The rate of reocclusion of the infarct-related vessel has been reported to be approximately 15-20%. The rate of reocclusion depends on dosage, additional anticoagulant therapy and residual stenosis. When the reinfarctions were evaluated in studies involving 8800 Streptokinase-treated patients, the overall rate was 3.8% (range 2-15%). In over 8500 control patients, the rate of reinfarction was 2.4%. However, the ISIS-2 study showed that an increase in reinfarction was avoided when Streptokinase was combined with low dose aspirin. The rate of reinfarction in the combination group was 1.8% vs. 1.9% in the group given aspirin alone.

Streptase, Streptokinase, administered by the intracoronary route has resulted in thrombolysis usually within one hour, and ensuing reperfusion results in improvement of cardiac function and reduction of mortality (5,6) . LVEF was increased in patients treated with Streptokinase when compared to patients treated with conventional therapy. When the initial LVEF was low, the Streptokinase-treated patients showed greater improvement than did the controls. Spontaneous reperfusion is known to occur and has been observed with angiography at various time points after infarction. Data from one study show that 73% of Streptokinase-treated patients and 47% of the placebo-allocated patients reperfused during hospitalization. The relationship between coronary artery patency and clinical efficacy has not been established.

Studies with thrombolytic therapy for pulmonary embolism show no significant difference in lung perfusion scan between the thrombolysis group and the heparin group at one-year follow-up. However, measurements of pulmonary capillary blood volumes and diffusing capacities at two weeks and one year after therapy indicate that a more complete resolution of thrombotic obstruction and normalization of pulmonary physiology was achieved with thrombolytic therapy, thus preventing the long term sequelae of pulmonary hypertension and pulmonary failure (7) .

The long term benefit of Streptase, Streptokinase, therapy for deep vein thrombosis (DVT) has been evaluated venographically (8) . The combined results of five randomized studies show no residual thrombotic material in 60-75% of patients treated with Streptokinase versus only 10% of those treated with heparin. Thrombolytic therapy also preserves venous valve function in a majority of cases, thus avoiding the pathologic venous changes that produce the clinical post-phlebitic syndrome which occurs in 90% of the DVT patients treated with heparin.

There is a time-related decrease in effectiveness when Streptase, Streptokinase, is used in the management of peripheral arterial thromboembolism. When administered three to ten days after onset of obstruction, rates of clearance of 50-75% were reported.

Acute Evolving Transmural Myocardial Infarction: Streptase, Streptokinase, is indicated for use in the management of acute myocardial infarction (AMI) in adults, for the lysis of intracoronary thrombi, the improvement of ventricular function, and the reduction of mortality associated with AMI, when administered by either the intravenous or the intracoronary route, as well as for the reduction of infarct size and congestive heart failure associated with AMI when administered by the intravenous route. Earlier administration of Streptokinase is correlated with greater clinical benefit. (See .)

Pulmonary Embolism: Streptase, Streptokinase, is indicated for the lysis of objectively diagnosed (angiography or lung scan) pulmonary emboli, involving obstruction of blood flow to a lobe or multiple segments, with or without unstable hemodynamics.

Deep Vein Thrombosis: Streptase, Streptokinase, is indicated for the lysis of objectively diagnosed (preferably ascending venography), acute, extensive thrombi of the deep veins such as those involving the popliteal and more proximal vessels.

Arterial Thrombosis or Embolism: Streptase, Streptokinase, is indicated for the lysis of acute arterial thrombi and emboli. Streptokinase is not indicated for arterial emboli originating from the left side of the heart due to the risk of new embolic phenomena such as cerebral embolism.

Occlusion of Arteriovenous Cannulae:   Streptase, Streptokinase, is indicated as an alternative to surgical revision for clearing totally or partially occluded arteriovenous cannulae when acceptable flow cannot be achieved.


Because thrombolytic therapy increases the risk of bleeding, Streptase, Streptokinase, is contraindicated in the following situations:

Streptokinase should not be administered to patients having experienced severe allergic reaction to the product.

Bleeding:   Following intravenous high-dose brief-duration Streptokinase therapy in acute myocardial infarction, severe bleeding complications requiring transfusion are extremely rare (0.3-0.5%), and combined therapy with low dose aspirin does not appear to increase the risk of major bleeding. The addition of aspirin to Streptokinase may cause a slight increase in the risk of minor bleeding (3.1% without aspirin vs. 3.9% with) (2) .

Streptokinase will cause lysis of hemostatic fibrin deposits such as those occurring at sites of needle punctures, particularly when infused over several hours, and bleeding may occur from such sites. In order to minimize the risk of bleeding during treatment with Streptokinase, venipunctures and physical handling of the patient should be performed carefully and as infrequently as possible, and intramuscular injections must be avoided.

Should an arterial puncture be necessary during intravenous therapy, upper extremity vessels are preferable. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding.

In the following conditions the risks of therapy may be increased and should be weighed against the anticipated benefits.

Should serious spontaneous bleeding (not controllable by local pressure) occur, the infusion of Streptase, Streptokinase, should be terminated immediately and treatment instituted as described under ADVERSE REACTIONS.

Bleeding into the pericardium, sometimes associated with myocardial rupture, has been seen in individual cases and has resulted in fatalities.

Arrhythmias:   Rapid lysis of coronary thrombi has been shown to cause reperfusion atrial or ventricular dysrhythmias requiring immediate treatment. Careful monitoring for arrhythmia is recommended during and immediately following administration of Streptase, Streptokinase, for acute myocardial infarction. Occasionally, tachycardia and bradycardia have been observed.

Hypotension:   Hypotension, sometimes severe, not secondary to bleeding or anaphylaxis has been observed during intravenous Streptase, Streptokinase, infusion in 1% to 10% of patients. Patients should be monitored closely and, should symptomatic or alarming hypotension occur, appropriate treatment should be administered. This treatment may include a decrease in the intravenous Streptokinase infusion rate. Smaller hypotensive effects are common and have not required treatment.

Cholesterol Embolism: Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism may include livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.

Other:   Non-cardiogenic pulmonary edema has been reported rarely in patients treated with Streptase, Streptokinase. The risk of this appears greatest in patients who have large myocardial infarctions and are undergoing thrombolytic therapy by the intracoronary route.

Rarely, polyneuropathy has been temporally related to the use of Streptase, Streptokinase, with some cases described as Guillain Barré Syndrome.

Should pulmonary embolism or recurrent pulmonary embolism occur during Streptase, Streptokinase, therapy, the originally planned course of treatment should be completed in an attempt to lyse the embolus. While pulmonary embolism may occasionally occur during Streptokinase treatment, the incidence is no greater than when patients are treated with heparin alone. In addition to pulmonary embolism, embolization to other sites during Streptase treatment, has been observed.


General:   There have been rare cases where Streptase, Streptokinase, has been administered for suspected AMI subsequently diagnosed as pancreatitis. Fatalities have occurred under these circumstances.

Repeated Administration -- Because of the increased likelihood of resistance due to antistreptokinase antibody, Streptase, Streptokinase, may not be effective if administered between five days and twelve months of prior Streptokinase or Anistreplase administration, or streptococcal infections, such as streptococcal pharyngitis, acute rheumatic fever, or acute glomerulonephritis secondary to a streptococcal infection.

Laboratory Tests

Intravenous or Intracoronary Infusion for Myocardial Infarction -- Intravenous administration of Streptase, Streptokinase, will cause marked decreases in plasminogen and fibrinogen and increases in thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT), which usually normalize within 12-24 hours. These changes may also occur in some patients with intracoronary administration of Streptokinase.

Intravenous Infusion for Other -- Before commencing thrombolytic therapy, it is desirable to obtain an activated partial thromboplastin time (APTT), a prothrombin time (PT), a thrombin time (TT), or fibrinogen levels, and a hematocrit and platelet count. If heparin has been given, it should be discontinued and the TT or APTT should be less than twice the normal control value before thrombolytic therapy is started.

During the infusion, decreases in plasminogen and fibrinogen levels and an increase in the level of FDP (the latter two causing a prolongation in the clotting times of coagulation tests) will generally confirm the existence of a lytic state. Therefore, lytic therapy can be confirmed by performing the TT, APTT, PT, or fibrinogen levels approximately 4 hours after initiation of therapy. If heparin is to be (re)instituted following the Streptase, Streptokinase, infusion, the TT or APTT should be less than twice the normal control value (see manufacturer's prescribing information for proper use of heparin).

Drug Interactions:    The interaction of Streptase, Streptokinase, with other drugs has not been well studied.

Use of Anticoagulants and Antiplatelet Agents -- Streptase, Streptokinase, alone or in combination with antiplatelet agents and anticoagulants, may cause bleeding complications. Therefore, careful monitoring is advised. In the treatment of acute MI, aspirin, when not otherwise contraindicated, should be administered with Streptokinase ( see below ).

Anticoagulation and Antiplatelets After Treatment for Myocardial Infarction -- In the treatment of acute myocardial infarction, the use of aspirin has been shown to reduce the incidence of reinfarction and stroke. The addition of aspirin to Streptokinase causes a minimal increase in the risk of minor bleeding (3.9% vs. 3.1%), but does not appear to increase the incidence of major bleeding (see ADVERSE REACTIONS ) (2) . The use of anticoagulants following administration of Streptokinase increases the risk of bleeding, but has not yet been shown to be of unequivocal clinical benefit. Therefore, whereas the use of aspirin is recommended unless otherwise contraindicated, the use of anticoagulants should be decided by the treating physician.

Anticoagulation After IV Treatment for Other -- Continuous intravenous infusion of heparin, without a loading dose, has been recommended following termination of Streptase, Streptokinase, infusion for treatment of pulmonary embolism or deep vein thrombosis to prevent rethrombosis. The effect of Streptokinase on thrombin time (TT) and activated partial thromboplastin time (APTT) will usually diminish within 3 to 4 hours after Streptokinase therapy, and heparin therapy without a loading dose can be initiated when the TT or the APTT is less than twice the normal control value.


Pregnancy Category C -- Animal reproduction studies have not been conducted with Streptase, Streptokinase. It is also not known whether Streptokinase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Streptokinase should be given to a pregnant woman only if clearly needed.

Pediatric Use:  

Controlled clinical studies have not been conducted in children to determine safety and efficacy in the pediatric population. The evidence of clinical benefits and risks is solely based on anecdotal reports in patients ranging in age from <1 month to 16 years. The largest number of patient reports have pertained to the use of streptokinase in arterial occlusions. For arterial occlusions the most frequently used loading dose was 1000 IU/kg; fewer numbers of patients received 3000 IU/kg. Loading dose durations have typically ranged from 5 minutes to 30 minutes. Continuous infusion doses were frequently 1000 IU/kg/hr; fewer were at 1500 IU/kg/hr. Infusions were maintained for </= 12 hours in approximately half of the published cases; a smaller proportion were between 12 hours and 24 hours. Reported adverse events associated with the use of streptokinase in the pediatric population are similar in nature to those associated with its use in adults. Rates of all bleeding complications have been variable, and as high as 50% at catheter sites in some studies. Occasionally bleeding has required transfusion. Careful monitoring of patient status is necessary.


The following adverse reactions have been associated with intravenous therapy and may also occur with intracoronary artery infusion:

Bleeding:   The reported incidence of bleeding (major or minor) has varied widely depending on the indication, dose, route and duration of administration, and concomitant therapy.

Minor bleeding can be anticipated mainly at invaded or disturbed sites. If such bleeding occurs, local measures should be taken to control the bleeding.

Severe internal bleeding involving gastrointestinal (including hepatic bleeding), genitourinary, retroperitoneal, or intracerebral sites has occurred and has resulted in fatalities. In the treatment of acute myocardial infarction with intravenous Streptokinase, the GISSI and ISIS-2 studies reported a rate of major bleeding (requiring transfusion) of 0.3-0.5%. However, rates as high as 16% have been reported in studies which required administration of anticoagulants and invasive procedures.

Major bleed rates are difficult to determine for other dosages and patient populations because of the different dosing and intervals of infusions. The rates reported appear to be within the ranges reported for intravenous administration in acute myocardial infarction.

Should uncontrollable bleeding occur, Streptokinase infusion should be terminated immediately, rather than slowing the rate of administration of or reducing the dose of Streptokinase. If necessary, bleeding can be reversed and blood loss effectively managed with appropriate replacement therapy. Although the use of aminocaproic acid in humans as an antidote for Streptokinase has not been documented, it may be considered in an emergency situation.

Allergic Reactions:   Fever and shivering, occurring in 1-4% of patients (1,2) , are the most commonly reported allergic reactions with intravenous use of Streptase, Streptokinase, in acute myocardial infarction. Anaphylactic and anaphylactoid reactions ranging in severity from minor breathing difficulty to bronchospasm, periorbital swelling or angioneurotic edema have been observed rarely. Other milder allergic effects such as urticaria, itching, flushing, nausea, headache and musculoskeletal pain have also been observed, as have delayed hypersensitivity reactions such as vasculitis and interstitial nephritis. Anaphylactic shock is very rare, having been reported in 0-0.1% of patients (1,2,4) .

Mild or moderate allergic reactions may be managed with concomitant antihistamine and/or corticosteroid therapy. Severe allergic reactions require immediate discontinuation of Streptase, Streptokinase, with adrenergic, antihistamine, and/or corticosteroid agents administered intravenously as required.

Respiratory   There have been reports of respiratory depression in patients receiving Streptokinase. In some cases, it was not possible to determine whether the respiratory depression was associated with Streptokinase or was a symptom of the underlying process. If respiratory depression is associated with Streptokinase, the occurrence is believed to be rare.

Other Adverse Reactions:   Transient elevations of serum transaminases have been observed. The source of these enzyme rises and their clinical significance is not fully understood.

There have been reports in the literature of cases of back pain associated with the use of Streptokinase. In most cases the pain developed during Streptokinase intravenous infusion and ceased within minutes of discontinuation of the infusion.


Acute Evolving Transmural Myocardial Infarction: Administer Streptokinase as soon as possible after onset of symptoms. The greatest benefit in mortality reduction was observed when Streptokinase was administered within four hours, but statistically significant benefit has been reported up to 24 hours (see ).

Route      Total Dose          Dosage/Duration
Intravenous  infusion   1,500,000 IU   1,500,000 IU within 60 min.

Intracoronary infusion

140,000 IU 20,000 IU by bolus followed by
2,000 IU/min. for 60 min.

Pulmonary Embolism, Deep Vein Thrombosis, Arterial Thrombosis or Embolism: Streptase, Streptokinase, treatment should be instituted as soon as possible after onset of the thrombotic event, preferably within 7 days. Any delay in instituting lytic therapy to evaluate the effect of heparin therapy decreases the potential for optimal efficacy. Since human exposure to streptococci is common, antibodies to Streptokinase are prevalent. Thus, a loading dose of Streptokinase sufficient to neutralize these antibodies is required. A dose of 250,000 IU of Streptokinase infused into a peripheral vein over 30 minutes has been found appropriate in over 90% of patients. Furthermore, if the thrombin time or any other parameter of lysis after 4 hours of therapy is not significantly different from the normal control level, discontinue Streptokinase because excessive resistance is present.

Indication Loading Dose IV Infusion
Pulmonary Embolism 250,000 IU/30 min. 100,000 IU/hr for 24 hr
(72 hrs if concurrent DVT is suspected).
Deep Vein Thrombosis 250,000 IU/30 min. 100,000 IU/hr for 72 hr
Arterial Thrombosis or Embolism 250,000 IU/30min. 100,000 IU/hr for 24-72 hr

Arteriovenous Cannulae Occlusion: Before using Streptase, Streptokinase, an attempt should be made to clear the cannula by careful syringe technique, using heparinized saline solution. If adequate flow is not re-established, Streptokinase may be employed. Allow the effect of any pretreatment anticoagulants to diminish. Instill 250,000 IU Streptokinase in 2 mL of solution into each occluded limb of the cannula slowly. Clamp off cannula limb(s) for 2 hours. Observe the patient closely for possible adverse effects. After treatment, aspirate contents of infused cannula limb(s), flush with saline, reconnect cannula.

Pediatric Patients:   Specific dosage and administration recommendations cannot be made based on the limited data available. However, published experience generally used loading and continuous infusion doses administered on a weight-adjusted basis. See Precautions, Pediatric Use.

Reconstitution and Dilution:    The protein nature and lyophilized form of Streptase, Streptokinase, require careful reconstitution and dilution. Slight flocculation (described as thin translucent fibers) of reconstituted Streptokinase occurred occasionally during clinical trials but did not interfere with the safe use of the solution. The following reconstitution and dilution procedures are recommended:

Vials and Infusion Bottles

  1. Slowly add 5 mL Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to the Streptase, Streptokinase, vial, directing the diluent at the side of the vacuum-packed vial rather than into the drug powder.
  2. Roll and tilt the vial gently to reconstitute. Avoid shaking. (Shaking may cause foaming.) (If necessary, total volume may be increased to a maximum of 500 mL in glass or 50 mL in plastic containers, and the infusion pump rate in Table 1 should be adjusted accordingly.) To facilitate setting the infusion pump rate, a total volume of 45 mL, or a multiple thereof, is recommended.
  3. Withdraw the entire reconstituted contents of the vial; slowly and carefully dilute further to a total volume as recommended in Table 1. Avoid shaking and agitation on dilution.
  4. When diluting the 1,500,000 IU infusion bottle (50 mL), slowly add 5 mL Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, directing it at the side of the bottle rather than into the drug powder. Roll and tilt the bottle gently to reconstitute. Avoid shaking as it may cause foaming. Add an additional 40 mL of diluent to the bottle, avoiding shaking and agitation. (Total volume = 45 mL). Administer by infusion pump at the rate indicated in Table 1.
  5. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. (The Albumin (Human) may impart a slightly yellow color to the solution.)
  6. The reconstituted solution can be filtered through a0.8 µ m or larger pore size filter.
  7. Because Streptase, Streptokinase, contains no preservatives, it should be reconstituted immediately before use. The solution may be used for direct intravenous administration within eight hours following reconstitution if stored at 2-8°C (36-46°F).
  8. Do not add other medication to the container of Streptase, Streptokinase.
  9. Unused reconstituted drug should be discarded.

Vial Size
1,500,000 45 mL
Infuse 45 mL within 60 min.
   B. Intracoronary Infusion
250,000 125 mL
  1. 20,000 IU bolus
1. Loading Dose of 10 mL
  2. 2,000 IU/minute for 60 minutes
2. Then 60 mL/hour
  A. 1. 250,000 IU loading dose over 30 minutes
1,500,000 90 mL
1. Infuse 30 mL/hour for 30 minutes
       2. 100,000 IU/hour maintenance dose
2. Infuse 6 mL per hour
1,500,000 infusion
45 mL
1. 15 mL/hour for 30 minutes
2. Infuse 3 mL per hour

For Use In Arteriovenous Cannulae:   Slowly reconstitute the contents of 250,000 IU Streptase, Streptokinase, vacuum-packed vial with 2 mL Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.


Streptase, Streptokinase, is supplied as a lyophilized white powder in 50 mL infusion bottles (1,500,000 IU) or in 6.5 mL vials with a color-coded label corresponding to the amount of purified Streptokinase in each vial as follows:

green    250,000 IU       NDC 0186-1770-01     box of 1

blue      750,000 IU       NDC 0186-1771-01     box of 1

red    1,500,000 IU       NDC 0186-1773-01     box of 1 (vials)

red    1,500,000 IU       NDC 0186-1774-01     box of 1 (infusion bottles)

Store unopened vials at controlled room temperature (15-30°C or 59-86°F).


  1. GISSI: Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet I: 397-402, 1986.
  2. ISIS-2 Collaborative Group: Randomized trial of streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet II:349-360, 1988.
  3. White, H., Norris, R., Brown, M., et al: Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 317: 850-5, 1987.
  4. The I.S.A.M. Study Group: A prospective trial of intravenous streptokinase in acute myocardial infarction (I.S.A.M.). N Engl J Med 314: 1465-1471, 1986.
  5. Anderson, J., Marshall, H., Bray, B., et al: A randomized trial of intracoronary streptokinase in the treatment of acute myocardial infarction. N Engl J Med 308: 1312-8, 1983.
  6. Kennedy, J., Ritchie, J., Davis, K., Fritz, J.: Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 309: 1477-82, 1983.
  7. Sharma, G., Burleson, V., Sasahara, A.: Effect of thrombolytic therapy on pulmonary-capillary blood volume in patients with pulmonary embolism. N Engl J Med 303: 842-5, 1980.
  8. Arnesen, H., Heilo, A., Jakobsen, E., et al: A prospective study of streptokinase and heparin in the treatment of venous thrombosis. Acta Med Scand 203: 457-463, 1978.

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Distributed by Astra USA, Inc., Westborough, MA 01581

021596R11                                               (Revised 9/98)