For an adult with acute ST‑elevation myocardial infarction, how should streptokinase be administered (dose, timing, adjunctive therapy), what are its contraindications, and when is rescue percutaneous coronary intervention indicated?

Streptokinase Administration in STEMI

Streptokinase should be administered as 1.5 million units IV over 30-60 minutes when primary PCI cannot be performed within 90-120 minutes of STEMI diagnosis, provided the patient presents within 12 hours of symptom onset and has no contraindications. 1

Dosing Regimen

• Standard dose: 1.5 million units in 100 mL of 5% dextrose or 0.9% saline infused over 30-60 minutes 1
• Research suggests lower doses (500,000-750,000 units over 30 minutes) may be equally effective with similar safety profiles, though this is not standard guideline-based practice 2
• The standard 1.5 million unit dose remains the guideline-recommended approach 1, 3

Timing Considerations

Initiate streptokinase as soon as possible after STEMI diagnosis, ideally within 30 minutes of hospital arrival (door-to-needle time). 1

• Pre-hospital administration is recommended when trained personnel are available and primary PCI cannot be performed within 120 minutes 1, 4
• Greatest benefit occurs when given within 6 hours of symptom onset 1, 3
• Can still be administered up to 12 hours after symptom onset in patients with persistent ST-elevation 1, 4

Mandatory Adjunctive Antiplatelet Therapy

Aspirin 150-325 mg should be chewed immediately (no enteric-coated formulation) if not already administered, followed by 75-100 mg daily indefinitely. 1

Clopidogrel 75 mg daily should be added to aspirin and continued throughout hospitalization. 1, 4

• If aspirin cannot be taken orally, administer 250 mg IV 1
• The combination of aspirin and clopidogrel reduces death, reinfarction, and stroke by approximately 9 events per 1000 patients treated 1

Adjunctive Anticoagulation

With streptokinase, heparin is optional but recommended for high-risk patients (anterior MI, heart failure, atrial fibrillation, or left ventricular thrombus). 1, 3

Anticoagulation Options:

• Unfractionated heparin (UFH): Weight-adjusted IV bolus followed by infusion for 24-48 hours, maintaining aPTT 50-70 seconds 1
• Subcutaneous UFH: 12,500 units twice daily is an acceptable alternative 3
• Enoxaparin: Not specifically studied with streptokinase but can be considered; dose adjustment required for patients ≥75 years or creatinine clearance <30 mL/min 1

Critical caveat: aPTT values >70 seconds are associated with increased mortality and bleeding—close monitoring is mandatory 1

Absolute Contraindications

Do not administer streptokinase if any of the following are present: 1

• Hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke within preceding 6 months
• Central nervous system damage or neoplasms
• Recent major trauma/surgery/head injury (within 3 weeks)
• Gastrointestinal bleeding within the last month
• Known bleeding disorder
• Aortic dissection
• Previous streptokinase or anistreplase administration (antibodies persist ≥10 years and impair efficacy) 1

Relative Contraindications

Consider risk-benefit ratio carefully with: 1

• Transient ischemic attack within 6 months
• Oral anticoagulant therapy
• Pregnancy or within 1 week postpartum
• Non-compressible puncture sites
• Traumatic resuscitation
• Refractory hypertension (systolic BP >180 mmHg)
• Advanced liver disease
• Infective endocarditis
• Active peptic ulcer

Assessment of Reperfusion Success

At 60-90 minutes after streptokinase initiation, measure ST-segment resolution in the lead with greatest initial ST-elevation. 1, 4

• Successful reperfusion: ≥50% ST-segment resolution 1, 4
• Failed reperfusion: <50% ST-segment resolution 1, 4
• Clinical signs of reperfusion include resolution of chest pain and reperfusion arrhythmias (though these are less reliable) 5

Rescue PCI Indications

Perform immediate rescue PCI when: 1, 4

• Failed fibrinolysis: <50% ST-segment resolution at 60-90 minutes 1, 4
• Hemodynamic instability or cardiogenic shock 1, 4
• Electrical instability (sustained ventricular arrhythmias) 1, 4
• Worsening ischemia or evidence of reocclusion 1, 4

All patients should be transferred to a PCI-capable center immediately after fibrinolysis for potential rescue or routine angiography. 1, 4

Routine Post-Fibrinolysis Management

After successful fibrinolysis (≥50% ST-segment resolution), perform angiography and PCI of the infarct-related artery within 2-24 hours. 1, 4

• Very early angiography (<2 hours) is not associated with increased bleeding or adverse outcomes 1
• Emergency angiography is indicated for heart failure, cardiogenic shock, or recurrent ischemia 1, 4

Critical Pitfalls to Avoid

• Never re-administer streptokinase: Antibodies persist for at least 10 years and can cause allergic reactions and treatment failure 1
• If re-occlusion occurs, use a non-immunogenic agent (alteplase, reteplase, or tenecteplase) or proceed directly to rescue PCI 1
• Monitor for hypotension during infusion: Streptokinase commonly causes transient hypotension; slow the infusion rate if this occurs 1
• Do not delay treatment for cardiac biomarkers: Treat based on clinical presentation and ECG findings 6

Why Fibrin-Specific Agents Are Preferred Over Streptokinase

While streptokinase is effective, fibrin-specific agents (tenecteplase, alteplase, reteplase) are preferred when available because: 1

• Tenecteplase and alteplase reduce mortality by an additional 10 deaths per 1000 patients compared to streptokinase 1
• Fibrin-specific agents achieve better coronary flow (TIMI 3 flow in 75% vs 38% with streptokinase) 7
• Single-bolus tenecteplase is easier to administer and associated with fewer non-cerebral bleeding complications 1
• However, streptokinase remains a reasonable option when cost and availability are limiting factors 1