Recommended Dosing Regimens for Thrombolysis with Alteplase (tPA)
For adult patients with acute ischemic stroke, the FDA-approved dose of alteplase is 0.9 mg/kg (maximum 90 mg), with 10% given as an intravenous bolus over 1 minute and the remaining 90% administered as an intravenous infusion over 60 minutes. 1
Adult Dosing by Indication
Acute Ischemic Stroke
- Timing: Administer within 3 hours of symptom onset; may extend to 4.5 hours with additional exclusion criteria
- Dose: 0.9 mg/kg (maximum 90 mg total)
- 10% as IV bolus over 1 minute
- 90% as IV infusion over 60 minutes
- Blood pressure target: <185/110 mmHg before treatment, <180/105 mmHg after treatment 2, 1
Acute Myocardial Infarction
Two FDA-approved regimens:
Accelerated Infusion:
- For patients >67 kg: 15 mg IV bolus, then 50 mg over first 30 min, followed by 35 mg over next 60 min
- For patients ≤67 kg: 15 mg IV bolus, then 0.75 mg/kg over first 30 min, followed by 0.5 mg/kg over next 60 min
- Maximum total dose: 100 mg 1
3-Hour Infusion:
- For patients ≥65 kg: 100 mg total (6-10 mg bolus, 50-54 mg over rest of first hour, 20 mg over second hour, 20 mg over third hour)
- For patients <65 kg: 1.25 mg/kg over 3 hours (0.075 mg/kg bolus, 0.675 mg/kg over rest of first hour, 0.25 mg/kg over second hour, 0.25 mg/kg over third hour) 1
Pulmonary Embolism
- Dose: 100 mg IV infusion over 2 hours
- Anticoagulation: Institute parenteral anticoagulation near the end of or immediately following the alteplase infusion when coagulation parameters normalize 1
Deep Vein Thrombosis (DVT)
- Systemic thrombolysis: FDA-approved adult dosing is 100 mg IV infused over 2 hours 3
- Catheter-directed thrombolysis (CDT): 0.5-1 mg/h for adults 3
Pediatric Dosing
Systemic Thrombolysis
- Standard dose: 0.5 mg/kg/hour over 6 hours (range: 0.1-0.5 mg/kg/hour over 2-6 hours)
- Low-dose regimens: 0.01-0.06 mg/kg/hour for 12-48 hours
- Recent standardized regimen: 0.03 mg/kg/hour for 48 hours (maximum 2 mg/kg/hour) 3
Catheter-Directed Thrombolysis
- DVT: 0.01-0.03 mg/kg/hour (maximum 2 mg/hour)
- Pulmonary embolism: 0.03-0.06 mg/kg/hour (maximum 2 mg/hour) 3
Special Populations and Considerations
Coronary Thrombosis in Children
Three strategies have been reported:
- 0.1-0.6 mg/kg/hour IV (commonly 0.5 mg/kg/hour) for 6 hours
- 0.2 mg/kg IV (maximum 15 mg), then 0.75 mg/kg over 30 min (maximum 50 mg), followed by 0.5 mg/kg over 60 min (maximum 35 mg); maximum total dose 100 mg
- Low-dose tPA combined with abciximab for Kawasaki disease 3
Concomitant Anticoagulation
- No consensus exists for concomitant use of heparin with thrombolysis
- In low-dose systemic thrombolysis or CDT, unfractionated heparin (UFH) is commonly used:
- Low-dose UFH (5-10 U/kg/hour) or therapeutic UFH
- LMWH is generally not recommended due to longer half-life and less reversibility 3
Monitoring and Safety
Bleeding Risk
- 10-40% of patients treated with alteplase experience major adverse events
- Bleeding risk is higher in patients with lower weight, longer therapy duration, greater decrease in fibrinogen, and failure of clot resolution 3
Laboratory Monitoring
- Monitor fibrinogen levels (maintain >100 mg/dL)
- Monitor platelet count (maintain >50,000/mm³)
- For stroke patients: neurological monitoring every 15 minutes for first 2 hours 2
Management of Complications
- No direct reversal agent exists for alteplase
- Antifibrinolytics (tranexamic acid, aminocaproic acid) can be effective treatments
- For hypofibrinogenemia: fresh frozen plasma or cryoprecipitate
- For bleeding: appropriate blood product transfusion 3
Practical Administration Tips
- Use within 8 hours of reconstitution (when stored at 2-30°C)
- May be administered as reconstituted at 1 mg/mL or diluted to 0.5 mg/mL with equal volume of 0.9% sodium chloride or 5% dextrose
- Avoid excessive agitation during dilution; mix by gentle swirling or slow inversion 1
The most recent evidence strongly supports prompt administration of thrombolysis in eligible patients, as earlier treatment leads to better outcomes with a clear time-dependent effect on efficacy 2.