What are the doses of streptokinase, tenecteplase, and alteplase (tissue plasminogen activator (tPA)) for thrombolysis?

Thrombolytic Dosing for Acute Thrombolysis

For acute ischemic stroke, use alteplase 0.9 mg/kg (maximum 90 mg) as a 10% bolus followed by 90-minute infusion, or tenecteplase as a single weight-based bolus (30 mg for <60 kg, 35 mg for 60-69 kg, 40 mg for 70-79 kg, 45 mg for 80-89 kg, 50 mg for ≥90 kg). 1, 2

Alteplase (tPA) Dosing by Indication

Acute Ischemic Stroke

• Standard regimen: 0.9 mg/kg IV (maximum 90 mg total dose) 1, 3
  • Administer 10% of total dose as initial bolus over 1 minute 2, 1
  • Infuse remaining 90% over 60 minutes 2, 1
• Time window: Proven effective up to 4.5 hours from symptom onset 3
• The accelerated 90-minute infusion protocol demonstrates superior outcomes compared to 3-hour infusions 4

Acute Myocardial Infarction

• Accelerated regimen (GUSTO protocol): 4
  • 15 mg IV bolus
  • 0.75 mg/kg over 30 minutes (maximum 50 mg)
  • 0.5 mg/kg over 60 minutes (maximum 35 mg)
  • Total maximum dose: 100 mg
• This accelerated regimen shows survival advantage over streptokinase 4

Pulmonary Embolism with Shock

• 100 mg IV infused over 2 hours (FDA-approved adult dose) 2
• Alternative regimen: 0.6 mg/kg as 15-minute bolus demonstrated 76% survival with acceptable bleeding risk 5

Deep Venous Thrombosis (DVT)

• Systemic thrombolysis: 100 mg IV over 2 hours (FDA-approved) 2
• Catheter-directed thrombolysis (CDT): 0.5-1 mg/hour for adults 2
• Low-dose CDT: 0.01 mg/kg/hour (maximum 20 mg/24 hours, up to 96 hours) 2

Coronary Artery Thrombosis (Kawasaki Disease)

• 0.5 mg/kg/hour IV for 6 hours (commonly used regimen) 2
• Alternative accelerated regimen: 2
  • 0.2 mg/kg IV bolus (maximum 15 mg)
  • 0.75 mg/kg over 30 minutes (maximum 50 mg)
  • 0.5 mg/kg over 60 minutes (maximum 35 mg)
  • Total maximum: 100 mg

Central Venous Catheter Dysfunction

• 2 mg intraluminal dwell for 30-60 minutes 2
• 2 mg dose superior to 1 mg dose (adjusted HR 2.75 for catheter removal with lower dose) 2

Pediatric Dosing (VTE)

• Standard-dose systemic: 0.5 mg/kg/hour over 6 hours (range 0.1-0.5 mg/kg/hour over 2-6 hours) 2
• Low-dose systemic: 0.01-0.06 mg/kg/hour for 12-48 hours 2
  • Most patients respond to 0.01-0.03 mg/kg/hour 2
  • Neonates require higher doses: 0.06 mg/kg/hour with FFP supplementation 2
• Pediatric CDT: 0.01-0.03 mg/kg/hour (maximum 2 mg/hour) 2

Tenecteplase Dosing

Acute Ischemic Stroke

• Weight-based single bolus: 1, 6
  • <60 kg: 30 mg
  • 60-69 kg: 35 mg
  • 70-79 kg: 40 mg
  • 80-89 kg: 45 mg
  • ≥90 kg: 50 mg
• Dose studied: 0.25 mg/kg shows superior recanalization for large vessel occlusions without increased hemorrhage 1, 6
• The 0.4 mg/kg dose shows no advantage over 0.25 mg/kg 6

Central Venous Catheter Dysfunction

• 2 mg intraluminal dwell for 1 hour 2
• Achieves 22% treatment success vs 5% with placebo (absolute difference 17%, P=0.004) 2

ST-Elevation Myocardial Infarction

• 0.5 mg/kg single bolus (regulatory approved dose, maximum 50 mg) 6

Streptokinase Dosing

Streptokinase should never be used for acute ischemic stroke due to unacceptably high hemorrhage rates. 1

For other indications where streptokinase remains in use (primarily in resource-limited settings):

• Acute MI: 1.5 million units IV over 60 minutes 4
• However, alteplase demonstrates superior 30-day survival compared to streptokinase in acute MI 4

Critical Safety Considerations

Bleeding Risk

• Major bleeding occurs in 10-40% of patients receiving tPA for VTE 2
• Risk factors for bleeding: lower weight, longer therapy duration, greater fibrinogen decrease, failed clot resolution 2
• Symptomatic intracranial hemorrhage: 2.4% with alteplase vs 0.2% placebo in stroke (3-4.5 hour window) 3

Reversal and Management

• No direct reversal agent exists for tPA 2
• Antifibrinolytics (tranexamic acid, aminocaproic acid) can be used 2
• Maintain fibrinogen >100 mg/dL and platelets >50,000/mm³ during therapy 2
• Administer FFP or cryoprecipitate for hypofibrinogenemia 2

Concomitant Anticoagulation

• Low-dose UFH (5-10 units/kg/hour) commonly used with low-dose systemic or CDT 2
• LMWH not recommended due to longer half-life and difficult reversibility 2
• For stroke: heparin administration more important with alteplase than streptokinase 4

Comparative Advantages

Tenecteplase vs Alteplase

• Single-bolus administration reduces nursing time and medication errors 1
• Longer half-life (90-130 minutes) vs alteplase 6
• Superior recanalization for large vessel occlusions (22% vs 10% substantial reperfusion) 1
• Noninferior clinical outcomes at 90 days with 0.25 mg/kg dose 1, 6
• No increase in symptomatic intracranial hemorrhage or mortality 6

Alteplase vs Streptokinase

• Lower mortality with accelerated alteplase regimen in acute MI 4
• Higher stroke risk with alteplase, particularly hemorrhagic stroke 4
• Cost differential: $32,678 per year of life saved with alteplase vs streptokinase 4