What is intermediate‑low‑risk pulmonary embolism?

Intermediate-Low-Risk Pulmonary Embolism

Intermediate-low-risk pulmonary embolism is a normotensive PE with evidence of either right ventricular dysfunction OR elevated cardiac biomarkers (but not both), indicating a moderate early mortality risk that requires hospitalization and close monitoring but not routine thrombolysis. 1

Definition and Classification Criteria

Intermediate-low-risk PE is defined by the following specific parameters 1:

• Hemodynamic stability: Systolic blood pressure ≥90 mmHg without vasopressor support and absence of shock 1
• Clinical risk score: PESI class III-V OR simplified PESI (sPESI) ≥1 1
• Imaging or biomarker findings: Evidence of EITHER right ventricular dysfunction on echocardiography/CT OR elevated cardiac biomarkers (troponin, NT-proBNP, BNP), but NOT both 1

This classification distinguishes intermediate-low-risk from intermediate-high-risk PE, where patients have BOTH RV dysfunction AND positive cardiac biomarkers, indicating substantially higher risk requiring more intensive monitoring 1.

Risk Stratification Framework

The European Society of Cardiology uses a hierarchical approach to classify PE severity 1:

• Step 1: Assess hemodynamic status—presence of shock or persistent hypotension (systolic BP <90 mmHg for >15 minutes) immediately classifies as high-risk PE 1
• Step 2: For normotensive patients, calculate PESI or sPESI score 1
• Step 3: Assess RV function via echocardiography or CT angiography (looking for RV dilatation with RV/LV ratio >0.9-1.0) 1
• Step 4: Measure cardiac biomarkers (troponin, NT-proBNP ≥600 ng/L, BNP, or H-FABP ≥6 ng/mL) 1

Patients with only ONE positive marker (either RV dysfunction OR elevated biomarkers) fall into the intermediate-low-risk category, while those with BOTH positive markers are intermediate-high-risk. 1

Prognostic Implications

The early mortality risk for intermediate-low-risk PE falls between low-risk (<1%) and intermediate-high-risk categories 1:

• Patients with intermediate-low-risk PE have an estimated 30-day mortality of 3-15% according to earlier ESC guidelines 1
• More recent data suggests these patients have lower mortality rates in the range of 1.8-3.8% when stratified by individual markers 1
• The presence of RV dysfunction alone (without biomarker elevation) carries an odds ratio of 4.19 for early death compared to patients without RV dysfunction 1

Clinical Management Approach

Immediate Anticoagulation

All intermediate-low-risk PE patients require prompt therapeutic anticoagulation with low molecular weight heparin (LMWH) or fondaparinux as first-line therapy. 1, 2

• LMWH (enoxaparin 1 mg/kg subcutaneously twice daily) or fondaparinux should be initiated immediately 2
• Unfractionated heparin is reserved for severe renal dysfunction (CrCl <30 mL/min) or high bleeding risk 1, 2
• Anticoagulation should begin before imaging confirmation if clinical probability is intermediate or high 2

Hospitalization and Monitoring

Intermediate-low-risk patients require hospital admission with close monitoring to detect early hemodynamic decompensation. 1, 3

• Continuous cardiac monitoring and serial vital sign assessment are essential 2, 3
• Repeat assessment of RV function and cardiac biomarkers should be considered if clinical deterioration occurs 3
• Oxygen supplementation should be provided to maintain SaO₂ >90% 3

Thrombolysis Decision-Making

Routine primary thrombolysis is NOT recommended for intermediate-low-risk PE due to bleeding risks outweighing benefits. 1, 4

The 2019 ESC guidelines explicitly state that systemic thrombolysis should NOT be given routinely to intermediate-risk patients, but should be reserved as rescue therapy if hemodynamic decompensation develops 1. This recommendation is based on evidence showing thrombolysis causes 65 additional major bleeding events per 1,000 patients and increases intracranial hemorrhage risk 3-4 fold 4.

Rescue thrombolysis should only be administered if the patient develops: 4, 3

• Persistent hypotension (systolic BP <90 mmHg)
• Requirement for vasopressor support
• Clinical signs of shock with end-organ hypoperfusion
• Progressive hemodynamic deterioration despite adequate anticoagulation

Transition to Oral Anticoagulation

Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for long-term management. 3

• Apixaban or rivaroxaban can be started without LMWH lead-in 3
• Dabigatran and edoxaban require initial parenteral anticoagulation before transitioning 3
• If warfarin is used, overlap with parenteral anticoagulation until INR reaches 2.0-3.0 2, 3
• Duration is typically 3 months for provoked PE and extended for unprovoked PE 2

Common Pitfalls and Caveats

Critical pitfall: Do not confuse intermediate-low-risk with low-risk PE 1. Patients with sPESI of 0 but evidence of RV dysfunction or elevated biomarkers should be classified as intermediate-risk (not low-risk) until the clinical implications are fully clarified 1. These patients require hospitalization and monitoring, not early discharge 1.

Avoid aggressive fluid resuscitation, which can worsen RV failure in the setting of RV dysfunction 3. If hypotension develops, vasopressor support with norepinephrine should be initiated rather than large-volume crystalloid administration 3.

Do not delay anticoagulation while awaiting complete diagnostic confirmation if clinical probability is intermediate or high 3. The risk of PE progression outweighs the bleeding risk of empiric anticoagulation in appropriate clinical scenarios 3.

Consider Pulmonary Embolism Response Team (PERT) consultation for borderline cases with progressive clinical deterioration, contraindications to thrombolysis, or severe RV dysfunction with refractory hypoxemia 3, 5.