When should alteplase (tissue plasminogen activator) be used instead of heparin for treating pulmonary embolism?

Alteplase vs Heparin in Pulmonary Embolism

Alteplase should be used instead of heparin alone in high-risk (massive) pulmonary embolism presenting with sustained hypotension, shock, or cardiac arrest, where it is the first-line treatment with a Class I, Level A recommendation. 1

Risk Stratification Determines Treatment Choice

The decision between alteplase and heparin hinges entirely on hemodynamic status and PE severity:

High-Risk (Massive) PE: Alteplase is Mandatory

Use alteplase 100 mg IV over 2 hours when any of the following are present: 2, 1

• Sustained hypotension (systolic BP <90 mmHg for ≥15 minutes)
• Cardiogenic shock requiring vasopressor support
• Pulselessness or cardiac arrest
• Persistent profound bradycardia (HR <40 bpm) with signs of shock

The mortality benefit is unequivocal in this population—untreated massive PE carries a 52.4% 90-day mortality compared to 8.1% in hemodynamically stable patients. 1, 3 Thrombolysis reduces death or recurrence significantly in high-risk PE. 2

For cardiac arrest or imminent arrest, give alteplase 50 mg as an immediate IV bolus over 2-15 minutes and continue CPR for at least 30 minutes to allow the drug to work. 1 Do not use the 100 mg infusion protocol during active arrest. 1

Intermediate-Risk (Submassive) PE: Heparin is Standard, Alteplase is Controversial

Use heparin alone (unfractionated or LMWH) as first-line treatment for hemodynamically stable patients, even if they have right ventricular dysfunction or elevated cardiac biomarkers. 2 Routine thrombolysis is not recommended in non-high-risk PE. 2

However, the evidence shows nuance: A randomized trial of 256 intermediate-risk patients found that alteplase plus heparin reduced the combined endpoint of death or clinical deterioration (10.2% vs 24.6%, P=0.004) compared to heparin alone, though mortality itself was not significantly different (3.4% vs 2.2%). 4 The benefit was driven by reduced need for rescue thrombolysis. 2, 4

Consider alteplase in carefully selected intermediate-risk patients who have both RV dysfunction on echo AND elevated cardiac biomarkers, particularly if they lack elevated bleeding risk. 2 The ESC notes that the risk/benefit ratio may be favorable in this subset, though a large European trial is ongoing to resolve this controversy. 2

Low-Risk PE: Heparin Only

Use LMWH or fondaparinux as the recommended initial treatment for hemodynamically stable patients without RV dysfunction. 2 Alteplase has no role here.

Critical Contraindication Considerations

In life-threatening massive PE, most traditional contraindications to thrombolysis should be overridden given the 52-65% mortality without treatment. 1 However, absolute contraindications still apply: 1

• Prior intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• Acute ischemic stroke within 6 months

When absolute contraindications exist, proceed immediately to surgical embolectomy or catheter-directed therapy rather than withholding reperfusion entirely. 2, 1

Anticoagulation Management Around Thrombolysis

Withhold heparin during the 2-hour alteplase infusion, then resume unfractionated heparin 3 hours after completion using weight-adjusted dosing (80 IU/kg bolus, then 18 IU/kg/hour targeting aPTT 1.5-2.5× control). 1, 3 One study suggests that weight-adjusted UFH followed by enoxaparin for 7 days after alteplase improves outcomes compared to standard UFH alone. 5

Diagnostic Confirmation

Imaging confirmation with CTPA is preferred before thrombolysis, but treatment must not be delayed in unstable patients. 1 High clinical suspicion combined with RV dysfunction on bedside echocardiography is sufficient to proceed with alteplase when the patient is too unstable for CT. 1 Do not perform pulmonary angiography before thrombolysis in unstable patients—it is time-consuming, hazardous, and increases bleeding risk. 1

Common Pitfalls to Avoid

• Do not use the 100 mg infusion in cardiac arrest—the 50 mg bolus is the correct regimen. 1
• Do not delay alteplase while awaiting imaging when cardiac arrest is imminent or the patient is in shock. 1
• Do not use alteplase routinely in intermediate-risk PE without careful risk-benefit assessment, as bleeding complications (including 2% intracranial hemorrhage) can occur. 2, 4
• Do not give aggressive fluid boluses in massive PE—this can worsen RV failure. 2

Bleeding Risk

Major bleeding occurs in 10-40% of patients receiving alteplase for PE, though no fatal or cerebral bleeding occurred in the landmark submassive PE trial. 1, 4 The risk must be weighed against the high mortality of untreated massive PE. 6