What is the standard dosing of streptokinase and tenecteplase (tissue plasminogen activator) for a patient with a history of cardiovascular disease presenting with ST-Elevation Myocardial Infarction (STEMI) undergoing thrombolytic therapy for the first time?

Standard Dosing of Streptokinase and Tenecteplase for First-Time Thrombolytic Therapy in STEMI

For first-time thrombolytic therapy in STEMI, administer streptokinase as 1.5 million units IV over 30-60 minutes, or preferably tenecteplase as a single weight-based IV bolus (30-50 mg based on body weight) over 5 seconds. 1, 2, 3

Tenecteplase Dosing (Preferred Agent)

Tenecteplase is the preferred fibrin-specific thrombolytic agent and should be administered as a single IV bolus over 5 seconds based on the following weight-based dosing: 1, 2, 4, 3

• <60 kg: 30 mg (6 mL) 1, 3
• 60 to <70 kg: 35 mg (7 mL) 1, 3
• 70 to <80 kg: 40 mg (8 mL) 1, 3
• 80 to <90 kg: 45 mg (9 mL) 1, 3
• ≥90 kg: 50 mg (10 mL) 1, 3

Tenecteplase Administration Details

• Reconstitute with 10 mL Sterile Water for Injection to achieve final concentration of 5 mg/mL 3
• Administer as single bolus over exactly 5 seconds via direct IV port 3
• Flush dextrose-containing lines with 0.9% sodium chloride before and after administration, as tenecteplase precipitates with dextrose 3
• Use immediately after reconstitution, or refrigerate at 2-8°C and use within 8 hours 3

Streptokinase Dosing (Alternative Agent)

Streptokinase should be administered as 1.5 million units IV over 30-60 minutes. 1

Important Streptokinase Considerations

• Absolute contraindication: Prior streptokinase or anistreplase use within the previous 6 months 1, 2
• The 30-minute accelerated infusion regimen (versus 60 minutes) achieves higher reperfusion rates (80% vs 58%) and faster reperfusion time (40 minutes vs 60 minutes) without increased major bleeding 5, 6
• Streptokinase is associated with higher mortality compared to newer fibrin-specific agents like tenecteplase 2, 7
• More likely to cause hypotension and allergic reactions compared to fibrin-specific agents 5

Mandatory Adjunctive Antiplatelet Therapy

All patients receiving thrombolytics must receive dual antiplatelet therapy immediately: 1, 2, 8

Aspirin Dosing

• Loading dose: 150-325 mg orally (chewable, non-enteric coated) OR 250-500 mg IV if oral not possible 1, 2
• Maintenance: 75-100 mg daily indefinitely 1, 2, 8

Clopidogrel Dosing (Age-Based)

• Age ≤75 years: 300 mg loading dose 1, 2, 8
• Age >75 years: 75 mg loading dose (no bolus) 1, 2, 8
• Maintenance: 75 mg daily for minimum 14 days, ideally up to 1 year 2, 8

Mandatory Adjunctive Anticoagulation

Anticoagulation must be continued for minimum 48 hours, preferably until revascularization or up to 8 days of hospitalization. 1, 2, 8

Enoxaparin (Preferred Agent)

Enoxaparin is preferred over unfractionated heparin, with age and renal-adjusted dosing: 1, 2, 8

• Age <75 years with normal renal function:

  • 30 mg IV bolus 1, 8
  • Then 1 mg/kg subcutaneous every 12 hours (maximum 100 mg for first 2 doses) 1, 8

• Age ≥75 years:

  • No IV bolus 1, 8
  • 0.75 mg/kg subcutaneous every 12 hours (maximum 75 mg for first 2 doses) 1, 8

• Contraindication: Creatinine clearance <30 mL/min 1

Unfractionated Heparin (Alternative)

• Initial bolus: 60 IU/kg IV (maximum 4000 IU) 1
• Infusion: 12 IU/kg/hour (maximum 1000 IU/hour) 1
• Monitor aPTT at 3,6,12, and 24 hours; target aPTT 50-70 seconds 1

Critical Timing Requirements

Thrombolytic therapy must be initiated within 30 minutes of first medical contact when primary PCI cannot be performed within 120 minutes. 1, 2

• Greatest benefit occurs within first 12 hours from symptom onset 1, 2, 4
• May consider between 12-24 hours if ongoing ischemia with large myocardium at risk or hemodynamic instability 2
• Pre-hospital administration is preferred when feasible 4

Post-Thrombolysis Management Protocol

All patients must be immediately transferred to a PCI-capable center after thrombolysis. 2, 8

Assessment at 60-90 Minutes

Evaluate ST-segment resolution to determine reperfusion success: 2, 8

• Successful reperfusion: ≥50% ST-segment resolution 2, 8
• Failed reperfusion (<50% ST-segment resolution): Proceed immediately to rescue PCI 2, 8

Rescue PCI Indications (Immediate)

• <50% ST-segment resolution at 60-90 minutes 2, 8
• Hemodynamic instability or cardiogenic shock 2, 8
• Electrical instability (ventricular arrhythmias) 2, 8
• Worsening ischemia or evidence of reocclusion 2, 8

Routine Angiography After Successful Thrombolysis

• Perform angiography and PCI of infarct-related artery between 2-24 hours after successful fibrinolysis 2, 4, 8

Absolute Contraindications to Thrombolytic Therapy

Do not administer thrombolytics if any of the following are present: 1, 2, 4

• Any prior intracranial hemorrhage 1, 2, 4
• Known structural cerebral vascular lesion (arteriovenous malformation) 1, 4
• Known malignant intracranial neoplasm (primary or metastatic) 1, 4
• Ischemic stroke within 3 months (EXCEPT acute ischemic stroke within 4.5 hours) 1, 4
• Suspected aortic dissection 1, 4
• Active bleeding or bleeding diathesis (excluding menses) 1, 4
• Significant closed-head or facial trauma within 3 months 1, 4
• Intracranial or intraspinal surgery within 2 months 1, 4
• Severe uncontrolled hypertension unresponsive to emergency therapy (SBP >180 mmHg or DBP >110 mmHg) 1, 4

Key Clinical Pitfalls to Avoid

• Never use dextrose-containing IV lines with tenecteplase without flushing with normal saline first, as precipitation will occur 3
• Do not use streptokinase if prior exposure within 6 months due to antibody formation rendering it ineffective 1, 2
• Do not omit anticoagulation after thrombolysis, as this dramatically increases reocclusion rates 1
• Do not delay transfer to PCI-capable center even if thrombolysis appears successful, as routine angiography is still indicated 2, 8
• Adjust enoxaparin dosing for elderly patients (>75 years) by eliminating the IV bolus and reducing subcutaneous dose to prevent bleeding complications 1, 8