What is the best approach for risk stratification and management of a patient with suspected pulmonary embolism (PE), particularly those with impaired renal function, bleeding disorders, or a history of cancer, heart failure, or chronic obstructive pulmonary disease (COPD)?

PE Risk Stratification

Stratify all patients with suspected or confirmed PE based on hemodynamic stability first, then further categorize hemodynamically stable patients into intermediate- and low-risk groups using validated clinical tools combined with biomarkers and imaging for right ventricular dysfunction. 1

Initial Assessment: Hemodynamic Status

The first critical step is identifying high-risk PE (previously termed "massive PE"), defined by the presence of shock or persistent hypotension with systolic blood pressure <90 mmHg. 1, 2

• High-risk patients require immediate aggressive intervention including systemic thrombolysis or surgical embolectomy, as they face early mortality rates justifying urgent reperfusion therapy. 1, 2
• In suspected high-risk PE, perform bedside echocardiography or emergency CTPA depending on availability, and initiate intravenous unfractionated heparin with weight-adjusted bolus injection without delay, even before imaging confirmation. 1, 2

Risk Stratification for Hemodynamically Stable Patients

For patients without hemodynamic instability, use a two-step approach combining clinical risk scores with assessment of right ventricular dysfunction and myocardial injury. 1, 3

Step 1: Clinical Risk Assessment

Use validated clinical prediction tools to estimate 30-day mortality risk:

• Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI) are the primary recommended tools for initial risk stratification. 3, 4, 5
• The Wells score and Geneva score can be used for clinical probability assessment, with neither demonstrating superiority over the other or clinician gestalt. 1
• For very low-risk patients, apply PERC (Pulmonary Embolism Rule-Out Criteria) to identify those in whom testing risks outweigh PE risk (approximately 1%), with pooled sensitivity of 97%. 1

Common pitfall: Do not measure D-dimers in patients with high clinical probability, as a normal result does not safely exclude PE. 1

Step 2: Assessment of RV Dysfunction and Myocardial Injury

For patients with intermediate clinical risk, further stratify into intermediate-high versus intermediate-low risk categories:

• Echocardiography: Look for moderate or severe right ventricular dilatation and hypokinesis, which represents the most useful imaging marker of high risk. 6
• Cardiac biomarkers: Elevated troponin levels indicate cardiac injury and right ventricular microinfarction, even without coronary artery disease. 6, 3
• Plasma lactate: Emerging as a sensitive marker of circulatory failure with promising prognostic accuracy. 3
• ECG findings: New right bundle branch block or T wave inversion in leads V1-V4 suggest right ventricular strain. 6

Intermediate-high risk patients have both RV dysfunction on imaging AND elevated cardiac biomarkers, placing them at increased risk for adverse outcomes. 3, 5

Special Populations Requiring Modified Approach

Impaired Renal Function

• Prefer ventilation-perfusion (V/Q) scanning over CTPA when contrast is contraindicated due to renal impairment. 1, 7
• However, be aware that V/Q scanning in patients with impaired renal function has limited positive predictive value (only 30% for high-probability scans), increasing to 72% when Wells score ≥7. 7
• D-dimer testing remains appropriate as an initial step in inpatients with renal impairment, as it maintains high sensitivity despite lower specificity in this population. 1
• Avoid NOACs in severe renal impairment; use vitamin K antagonists or adjust anticoagulation based on creatinine clearance. 1, 8

Cancer, Heart Failure, and COPD

These comorbidities are independent clinical risk factors for adverse outcomes and should elevate concern during risk stratification. 6

• Increasing age, cancer, congestive heart failure, and COPD all predict higher mortality risk. 6
• The Geneva Prognostic Score incorporates rapid clinical assessment of these factors. 6
• Consider these patients at higher baseline risk even with intermediate clinical scores. 4

Bleeding Disorders

• Absolute contraindication to thrombolysis in patients with high bleeding risk, particularly those susceptible to intracranial hemorrhage. 2, 6
• The intracranial hemorrhage rate with thrombolysis reached 3.0% in large registries. 6
• For high-risk PE patients with bleeding contraindications, surgical or catheter-based embolectomy becomes the preferred intervention. 1, 2

Risk-Based Management Algorithm

High-Risk PE (Hemodynamically Unstable)

• Immediate systemic thrombolysis (alteplase 0.6 mg/kg over 15 minutes, maximum 50 mg, or 100 mg over 2 hours). 2
• If thrombolysis contraindicated or fails: surgical pulmonary embolectomy. 1, 2
• Unfractionated heparin as initial anticoagulant (5,000-10,000 unit bolus, then 400-600 units/kg/day continuous infusion). 2, 9

Intermediate-High Risk PE

• Hospital admission to monitored unit. 3, 5
• Consider reduced-dose thrombolysis or catheter-directed therapy in selected patients, though evidence remains evolving. 3
• Standard anticoagulation with close monitoring for deterioration. 1
• Rescue thrombolysis if hemodynamic deterioration occurs despite anticoagulation. 1, 8

Intermediate-Low and Low-Risk PE

• Low-risk patients can be safely managed with ambulatory anticoagulation using tools like the Hestia criteria to identify suitable candidates. 3, 4, 5
• Prefer LMWH or fondaparinux over UFH for initial parenteral anticoagulation in stable patients. 1, 8
• Transition to NOACs (preferred) or vitamin K antagonists for long-term therapy. 1, 8

Critical Monitoring Parameters

• Physical examination: Distended jugular veins and right-sided S3 gallop indicate right ventricular failure. 6
• Serial assessment: Monitor for progressive worsening of RV function despite anticoagulation, which signals need for escalation. 6
• Age-adjusted D-dimer cutoffs (age × 10 ng/mL for patients >50 years) maintain >97% sensitivity while significantly increasing specificity. 1