Alteplase Administration Protocol
For massive pulmonary embolism with hemodynamic instability, administer 100 mg alteplase as a continuous IV infusion over 2 hours via peripheral vein, without an initial bolus, and withhold heparin during the infusion. 1, 2
Pre-Administration Assessment
Confirm hemodynamic instability with sustained hypotension (systolic BP <90 mmHg), shock index >1.0, or evidence of respiratory failure 1. If the patient is too unstable for imaging, proceed based on high clinical suspicion combined with bedside echocardiography showing RV dysfunction 1, 2.
Absolute Contraindications
- Active bleeding 3
- Recent stroke (within 3 months) 3
- Current gastrointestinal hemorrhage 3
- History of intracranial hemorrhage 3
- Recent intracranial/spinal surgery (within 3 months) 3
- Severe head trauma (within 3 months) 3
- Platelets <100,000/mm³, INR >1.7, aPTT >40 seconds, or PT >15 seconds 3
- Therapeutic dose of LMWH within previous 24 hours 3, 4
- Direct thrombin inhibitors or factor Xa inhibitors within 48 hours (unless appropriate laboratory tests are normal) 3
Relative Contraindications
In life-threatening massive PE, most relative contraindications should be reconsidered given the high mortality without treatment 3, 1, 4. These include:
- Recent surgery (within 7 days) 3, 2
- Peptic ulcer disease 3, 2
- Prolonged cardiopulmonary resuscitation 3, 2
- Structural GI malignancy or GI bleed within 21 days 3
Standard Dosing Protocols
Massive PE (Hemodynamically Unstable)
Primary regimen: 100 mg alteplase as continuous IV infusion over 2 hours via peripheral vein 1, 2. This is the FDA-approved regimen for massive PE 1.
Emergency bolus regimen: For cardiac arrest or rapidly deteriorating condition, administer 50 mg alteplase as immediate IV bolus, then reassess at 30 minutes 1, 2. This accelerated approach is reserved for imminent cardiovascular collapse 2.
Hemodynamically Stable Patients with Confirmed Massive PE
Consider 100 mg alteplase over 90 minutes (accelerated MI regimen) 1, 2. However, the mortality benefit of thrombolysis is established specifically for hemodynamically unstable patients 1.
Pediatric Dosing
Systemic thrombolysis: 0.1-0.6 mg/kg/hour IV for 6 hours (commonly 0.5 mg/kg/hour) 3. Alternative regimen: 0.2 mg/kg IV bolus (maximum 15 mg), then 0.75 mg/kg over 30 minutes (maximum 50 mg), followed by 0.5 mg/kg over 60 minutes (maximum 35 mg), with maximum total dose 100 mg 3, 2.
Neonates: May require higher doses at 0.06 mg/kg/hour with fresh frozen plasma (FFP) supplementation due to low plasminogen levels 1.
Catheter-Directed Thrombolysis
Adult dosing: 0.5-1 mg/hour via catheter 1. Multiple infusion durations are effective, with protocols ranging from 8 mg over 2 hours to 24 mg over 6 hours 1.
Pediatric dosing: 0.01-0.03 mg/kg/hour (maximum 2 mg/hour) for catheter-directed therapy 1. Alternative regimen: 0.025 mg/kg/hour or 0.5-2 mg/hour every 12-24 hours 3.
Dwell time: For catheter-directed thrombolysis, alteplase should dwell in the lungs for 2-6 hours before opening the pigtail catheter, with most protocols using 4-6 hours as standard duration 1.
Concurrent Anticoagulation Management
During alteplase infusion: Withhold heparin during the 2-hour infusion period per FDA recommendation 1, 2. For catheter-directed therapy, low-dose unfractionated heparin (5-10 U/kg/hour) may be used concurrently, maintaining activated clotting time around 250 seconds 1.
After alteplase completion: Resume therapeutic anticoagulation after completion of the infusion 1, 2. For systemic thrombolysis, resume unfractionated heparin 3 hours after completion using weight-adjusted dosing 2. Increase heparin to age-appropriate dose: ≥12 months = 20 μg/kg/hour; <12 months = 28 μg/kg/hour 3.
Pre-Treatment Preparation
Administer FFP 10-20 mL/kg before alteplase infusion as a plasminogen source 3. This is particularly important in pediatric patients and neonates with low baseline plasminogen levels 1.
Maintain fibrinogen >100 mg/dL and platelets >50,000/mm³ throughout treatment 3.
Monitoring Requirements
Prepare for bleeding complications occurring in 10-40% of patients 1, 2. Major hemorrhage requiring transfusion occurs in 20-30% of cases, while minor bleeding occurs in 54-68% 3.
Monitor continuously for signs of major bleeding, particularly intracranial hemorrhage, which is the most feared complication 3. However, recent evidence suggests low-dose alteplase (0.6 mg/kg, maximum 50 mg) may reduce bleeding risk without compromising efficacy 5.
Reassess hemodynamic status frequently during and after infusion 3. Improvement in RV dysfunction should be evident within 24-48 hours 1.
Reversal Strategy
Alteplase is reversible with aminocaproic acid (Amicar) if major bleeding occurs 3. The half-life of alteplase is only 4 minutes, allowing relatively rapid cessation of fibrinolytic activity after discontinuation 3.
Critical Clinical Pitfalls
Do not delay treatment waiting for imaging in hemodynamically unstable patients 4. If cardiac arrest is imminent, treat based on clinical grounds and bedside echocardiography findings 4, 2.
Do not confuse stroke and PE protocols: The stroke protocol uses 0.9 mg/kg (maximum 90 mg) over 60 minutes with 10% given as initial bolus, which differs significantly from the PE protocol 2.
Do not use alteplase as routine screening treatment without reasonable suspicion of PE 1. The mortality benefit is established specifically for massive PE with hemodynamic compromise 1.
Distinguish between catheter-directed thrombolysis for PE (hours-long infusion) and alteplase for clearing occluded catheters (30-120 minute dwell time) 1.