What is the role of tenecteplase (tissue plasminogen activator) in treating patients with acute pulmonary embolism, particularly those who are hemodynamically unstable or have evidence of right ventricular dysfunction?

Tenecteplase in Pulmonary Embolism

Tenecteplase should be administered immediately in hemodynamically unstable PE (massive PE with shock or sustained hypotension <90 mmHg), but should NOT be routinely used in hemodynamically stable patients, even those with right ventricular dysfunction, due to increased bleeding risk without proven mortality benefit.

Massive PE (Hemodynamically Unstable)

Administer tenecteplase as first-line therapy when systolic blood pressure is <90 mmHg for at least 15 minutes or the patient requires inotropic support. 1

Dosing Protocol

• Standard dosing: Weight-adjusted single bolus (same as for acute MI) or 100 mg alteplase over 2 hours via peripheral IV 2, 1
• Cardiac arrest/rapidly deteriorating: 50 mg alteplase as IV bolus 1
• Anticoagulation management: Withhold heparin during the 2-hour infusion, then resume at 1280 IU/hour when APTT is less than twice the upper limit of normal 1

Evidence Supporting Use

• Meta-analysis of hemodynamically unstable patients showed significant reduction in combined endpoint of death or recurrent PE (9.4% vs 19%; OR 0.45) 2
• This represents the only patient population where thrombolytics demonstrate mortality benefit 2

When Imaging is Unavailable

• In unstable patients with high clinical suspicion of PE, consider thrombolysis based on bedside echocardiography showing RV dysfunction as indirect evidence 2
• This approach is justified when patient instability precludes CT imaging 2, 1

Submassive PE (Hemodynamically Stable with RV Dysfunction)

Do NOT routinely administer tenecteplase in hemodynamically stable patients, even with RV dysfunction on echocardiography or elevated biomarkers. 2

Critical Evidence Against Routine Use

• Three meta-analyses found no decrease in mortality in unselected hemodynamically stable patients treated with thrombolytics 2
• While thrombolytics improve RV function and pulmonary perfusion more rapidly, these improvements have not translated to decreased mortality 2
• The PEITHO trial showed reduced hemodynamic decompensation (2.6% vs 5.6%) but significantly increased major bleeding (6.3% vs 1.2%) and stroke (2.4% vs 0.2%) 2
• Number needed to harm: 27 patients for major bleeding, 91 patients for intracranial hemorrhage 3
• Number needed to treat to prevent one death: 125 patients 3

Controversial Exception: Highly Selected Cases

Consider tenecteplase ONLY in hemodynamically stable patients who meet ALL of the following criteria 2, 1:

• Evidence of shock or respiratory failure (shock index >1.0, SaO₂ <95% with respiratory distress, altered mental status)
• Moderate to severe RV strain (RV hypokinesis, estimated RVSP >40 mmHg, clearly elevated troponin or BNP >100 pg/mL)
• No contraindications to fibrinolysis
• Clinical judgment suggests imminent decompensation

This remains controversial and is not standard practice. 2

Special Populations

Right Heart Thrombus

• Mortality rate 21% vs 11% without right heart thrombus 2
• No mortality difference between thrombolytic therapy and heparin alone (20.8% vs 23.5%), though selection bias limits interpretation 2
• Consider thrombolysis on case-by-case basis given high baseline mortality 2

Cancer Patients

• Same principles apply: use in hemodynamically unstable PE, avoid in stable patients 2
• Consider embolectomy as alternative when contraindications exist 2

Contraindications

Absolute Contraindications 1

• Recent hemorrhage
• Stroke
• Current gastrointestinal hemorrhage

Relative Contraindications 1

• Peptic ulcer disease
• Surgery within preceding 7 days
• Prolonged cardiorespiratory resuscitation

Key Clinical Pitfalls

Common mistake: Treating hemodynamically stable patients with RV dysfunction based on echocardiographic findings alone. The Becattini trial showed improved RV function at 24 hours with tenecteplase but was underpowered to detect differences in clinical outcomes and was prematurely terminated 2. The subsequent PEITHO trial confirmed no mortality benefit with significantly increased bleeding 2.

Critical distinction: The presence of RV dysfunction on echo does NOT automatically warrant thrombolysis unless the patient is hemodynamically unstable or showing signs of imminent decompensation 2.

Diagnostic confirmation: Always confirm PE with imaging (CTPA or V/Q scan) before thrombolysis when feasible 1. Only proceed without imaging confirmation in unstable patients who cannot be safely transported 2, 1.

Alternative Approaches

When thrombolysis is contraindicated or fails:

• Catheter-directed interventions: Consider in massive or submassive PE when systemic thrombolysis contraindicated or unsuccessful 2
• Surgical embolectomy: Category 2B recommendation for massive PE with contraindications to thrombolysis 2
• IVC filters: Only for patients with absolute contraindications to anticoagulation; retrievable filters preferred 2