Can alteplase (tissue plasminogen activator) be given to a patient with acute pulmonary embolism (PE) as a 10mg bolus followed by a 90mg infusion?

Alteplase Dosing for Pulmonary Embolism: The 10mg Bolus + 90mg Infusion Protocol is NOT Standard

No, the 10mg bolus followed by 90mg infusion protocol should NOT be used for pulmonary embolism—this is the stroke dosing regimen and represents a critical medication error if applied to PE patients. 1, 2

Critical Distinction: Stroke vs. PE Protocols

The confusion arises because alteplase has completely different dosing protocols depending on the indication:

For Stroke (NOT for PE):

• 0.9 mg/kg (maximum 90 mg) over 60 minutes, with 10% given as a bolus over 1 minute 3
• This is the protocol you're asking about, but it is explicitly contraindicated for PE 1

For Massive Pulmonary Embolism (Correct Protocol):

• 100 mg alteplase as a continuous IV infusion over 2 hours with NO initial bolus 1, 2, 4
• This is the FDA-approved and guideline-recommended regimen from the American Heart Association and American College of Cardiology 2
• Anticoagulation with heparin should be withheld during the 2-hour infusion period 2

Alternative PE Dosing Regimens by Clinical Scenario

For Cardiac Arrest or Rapidly Deteriorating Patients:

• 50 mg alteplase as IV bolus may be considered for life-threatening situations 1, 2, 4
• This represents a different emergency protocol when immediate action is required 4

For Hemodynamically Stable Patients with Confirmed Massive PE:

• 100 mg over 90 minutes (accelerated MI regimen) may be used 1, 2
• This involves a 15 mg IV bolus, followed by 50 mg IV over 30 minutes, then 35 mg IV over the next 60 minutes 3

Historical Context from Research:

• One older study (1992) did use 10 mg bolus followed by 90 mg over 2 hours in PE patients, showing angiographic improvement but with high bleeding rates (14 of 20 patients) 5
• However, this regimen has been superseded by current guidelines favoring the continuous 100 mg infusion without bolus 1, 2

Clinical Decision Algorithm

Step 1: Confirm Massive PE

• Sustained hypotension (SBP <90 mmHg for ≥15 minutes), shock index >1.0, or respiratory failure 1, 4
• Imaging confirmation preferred (CTPA), but may proceed with high clinical suspicion and RV dysfunction on bedside echo if patient too unstable 1, 4

Step 2: Assess Contraindications

• Absolute: Active bleeding, recent stroke, current GI hemorrhage 1, 4
• Relative: Recent surgery (within 7 days), peptic ulcer disease, prolonged CPR 1, 4
• In life-threatening massive PE, most relative contraindications should be ignored given high mortality without treatment 2, 4

Step 3: Select Appropriate Regimen

• Standard massive PE: 100 mg continuous IV infusion over 2 hours (no bolus) 1, 2, 4
• Cardiac arrest/extreme instability: 50 mg IV bolus 1, 2, 4
• Never use the stroke protocol (10mg bolus + 90mg infusion) for PE 1

Step 4: Anticoagulation Management

• Withhold heparin during the 2-hour alteplase infusion 2, 4
• Resume therapeutic anticoagulation after completion (typically heparin 1280 IU/hour when APTT <2× upper limit of normal) 4

Common Pitfalls to Avoid

• Do not confuse stroke and PE dosing protocols—the 10mg bolus + 90mg infusion is exclusively for stroke 3, 1
• Do not give an initial bolus for standard massive PE treatment—the approved regimen is continuous infusion only 1, 2
• Prepare for bleeding complications, which occur in 10-40% of patients receiving thrombolysis for PE 1, 2
• Major bleeding occurred in 15% of patients in studies using bolus regimens 1

Evidence Quality

The recommendation for 100 mg continuous infusion over 2 hours comes from the highest quality guideline evidence from the American Heart Association, American College of Cardiology, and American College of Chest Physicians 1, 2, 4. While older research studies explored various dosing regimens including bolus protocols 6, 7, 5, current consensus strongly favors the continuous infusion approach for standard massive PE management 1, 2.