Is a high Pulmonary Embolism Severity Index (PESI) score a warrant for thrombolysis in pulmonary embolism (PE)?

PESI Score Alone Does Not Warrant Thrombolysis in Pulmonary Embolism

A high PESI score is NOT an indication for thrombolysis in pulmonary embolism. Thrombolysis decisions must be based on hemodynamic status and evidence of right ventricular dysfunction, not risk stratification scores like PESI, which were designed to predict mortality and identify low-risk patients suitable for outpatient management—not to guide reperfusion therapy 1, 2.

Understanding PESI's Intended Purpose

PESI was derived and validated to predict 30-day mortality in PE patients, specifically to identify low-risk patients (Class I/II) who could be safely managed as outpatients 3. The score comprises independent predictors of mortality including age, comorbidities, vital signs, and oxygen saturation 3. PESI was never designed or validated as a tool to determine which patients require thrombolysis 3.

• Low-risk PESI patients (Class I/II) have 30-day mortality ≤1.6-3.6% and are candidates for outpatient management 3
• High-risk PESI patients (Class III-V) have higher mortality rates but this alone does not indicate need for thrombolysis 4

When Thrombolysis Is Actually Indicated

Thrombolysis should be reserved exclusively for high-risk PE with hemodynamic instability, defined as systolic blood pressure <90 mmHg, requirement for vasopressor support, or persistent hypotension with signs of shock 1, 2, 5.

Absolute Contraindication in Stable Patients

The European Society of Cardiology provides a Class III recommendation (meaning "do not use") against thrombolytic therapy in low-risk PE 1. Similarly, the American College of Chest Physicians and NICE explicitly recommend against routine thrombolysis in hemodynamically stable patients, regardless of PESI score 2.

Critical evidence against using PESI for thrombolysis decisions:

• Thrombolysis causes 65 more major bleeding events per 1,000 patients 2
• Intracranial hemorrhage risk increases 3-4 fold, resulting in 7 more ICH per 1,000 patients 2
• These bleeding risks outweigh any mortality benefit in hemodynamically stable patients 2

Correct Risk Stratification Approach

For Hemodynamically Stable Patients

The proper algorithm for stable PE patients (regardless of PESI score):

1. Initiate immediate anticoagulation with LMWH, fondaparinux, or NOACs—do not delay for imaging if clinical probability is intermediate/high 1, 5

2. Assess for right ventricular dysfunction using:

   • RV:LV ratio on CT imaging 1
   • Echocardiographic assessment of RV function 1
   • Cardiac biomarkers (troponin, BNP, NT-proBNP) 3, 1

3. Risk stratify using validated scores (PESI, sPESI, or Hestia criteria) to determine disposition—outpatient vs. inpatient monitoring 3, 1

When to Consider Thrombolysis in Initially Stable Patients

Reserve thrombolysis only for the rare stable patient who demonstrates clinical deterioration despite adequate anticoagulation 2:

• Decreasing systolic blood pressure with signs of shock 2
• Increasing heart rate with inadequate end-organ perfusion 2
• Worsening gas exchange or respiratory failure 2
• Progressive RV dysfunction on repeat imaging 2
• Rising cardiac biomarkers 2

Common Pitfalls to Avoid

Do not use RV dysfunction alone as an indication for thrombolysis in stable patients, even if they have a high PESI score—this significantly increases bleeding risk without proven mortality benefit 2. The presence of RV dysfunction in an otherwise stable patient with low PESI may warrant inpatient observation and biomarker monitoring, but not thrombolysis 1.

Do not confuse risk stratification with treatment escalation. A high PESI score (Class III-V) indicates higher mortality risk and need for inpatient management, but the treatment remains anticoagulation unless hemodynamic instability develops 3, 1, 4.

Evidence on PESI Performance

While PESI effectively predicts mortality (AUC 0.77-0.87), studies show it has limitations for predicting short-term clinical deterioration 3, 6. In one study, 14% of patients who had adverse clinical events within 5 days were categorized by PESI as low-risk 6. This underscores that PESI identifies patients safe for discharge, not patients requiring aggressive intervention 6, 7.

The modified sPESI score (score of 0 = low risk) identifies patients with 30-day mortality rates of 0.5-1.1% and low bleeding/recurrence rates, making them suitable for early discharge or home treatment 3, 7. This is the opposite clinical scenario from thrombolysis candidacy 7.