Pulmonary Embolism (PE)

Definition & Overview

Pathophysiology

• Mechanical obstruction raises pulmonary vascular resistance, increasing right ventricular (RV) afterload
• RV dilation and dysfunction follow, causing septal shift and impairing left ventricular filling
• Decreased cardiac output -> systemic hypotension -> cardiovascular collapse in severe cases
• Neurohormonal mediators (serotonin, histamine, thromboxane A2) cause additional vasoconstriction

• Dead space ventilation increases (perfused but not ventilated alveoli)
• Hypoxemia from V/Q mismatch, shunting, and reduced mixed venous O2 saturation
• Pulmonary infarction occurs in ~10% of cases, typically from peripheral emboli in patients with limited collateral supply

Risk Factors (Virchow's Triad)

Clinical Presentation

• Dyspnea - most common (75-80% of patients); notably absent in ~25%, so its absence does not rule out PE
• Chest pain - second most common; may be pleuritic (sharp, worsens with breathing) - only present in ~20% of PE cases and indicates peripheral embolism with pulmonary infarction
• Hemoptysis - associated with pulmonary infarction
• Unilateral leg swelling - present in <30% of patients but relatively specific when accompanying dyspnea/chest pain
• Syncope - seen in <5% of PE presentations; unexplained syncope with risk factors warrants PE workup
• Palpitations, fatigue, nonspecific malaise

• Shock index >1 (heart rate > systolic BP)
• Overt respiratory distress
• Syncope or seizure-like activity
• Pulseless electrical activity (PEA) arrest

Fever due to PE is typically low-grade; temperature >38.6°C (101.5°F) should suggest infection rather than infarction. - Rosen's Emergency Medicine, p. 1202

Diagnosis

Step 1: Pre-Test Probability (PTP) Assessment

• Score ≤4: Low probability (PE unlikely)
• Score >4: High probability (PE likely)

• Age >65: 1 | Prior PE/DVT: 3 | Recent surgery/immobilization: 2 | Active cancer: 2
• Unilateral leg pain: 3 | Hemoptysis: 2 | HR 75-94: 3, HR ≥95: 5 | Unilateral leg edema + pain on palpation: 4
• Low: 0-3 | Intermediate: 4-10 | High: >10

Step 2: PERC Rule (for LOW pre-test probability patients)

1. Age <50
2. Pulse <100
3. SaO2 >94%
4. No unilateral leg swelling
5. No hemoptysis
6. No recent trauma or surgery
7. No prior PE/DVT
8. No hormone use

Step 3: D-Dimer

• Sensitivity: 95-98%, Specificity: 40-55%
• A negative D-dimer in a patient with low-to-intermediate PTP effectively rules out PE
• Age-adjusted D-dimer cutoff: (Age × 10 µg/L) in patients >50 years - increases specificity without significant loss of sensitivity
• D-dimer is NOT useful in high-PTP patients (proceed directly to imaging)
• Elevated in many conditions: pregnancy, surgery, trauma, infection, malignancy - reducing specificity in hospitalized patients

Step 4: Imaging

• Sensitivity ~83%, specificity ~96% for PE
• Can visualize thrombus to the segmental level
• Also evaluates for RV dilation (prognostic indicator)
• Preferred in most non-pregnant patients

• Preferred in pregnancy (lower fetal radiation: ~0.011-0.022 cGy vs. CTPA)
• Also preferred in patients with contrast allergy or renal insufficiency
• Interpreted as: Normal (excludes PE), Low/Intermediate/High probability
• Diagnostic when high-probability scan + high clinical probability

• Can confirm DVT and support PE diagnosis without CT in selected patients

• RV dilation (RV:LV ratio >0.9), septal flattening ("D sign"), reduced TAPSE
• Not diagnostic but critical for risk stratification and hemodynamic assessment
• A negative bedside echo does not rule out PE

ECG & CXR Findings

• Sinus tachycardia (most common)
• S1Q3T3 pattern (classic but insensitive)
• New right bundle branch block
• Right axis deviation
• T-wave inversions in V1-V4

• Hampton's hump - wedge-shaped pleural-based opacity (pulmonary infarct)
• Westermark sign - oligemia distal to obstructed vessel
• Fleischner sign - dilated central pulmonary artery

Risk Stratification

Treatment

Anticoagulation (cornerstone of therapy)

• Apixaban (10 mg BID x7 days, then 5 mg BID) and rivaroxaban (15 mg BID x21 days, then 20 mg OD) are now first-line for most patients
• DOACs are preferred over warfarin for VTE treatment (equal or better efficacy, less bleeding)
• For IV UFH: weight-based dosing; many patients remain subtherapeutic in the first 24-48 hours
• Note on subsegmental PE: anticoagulation may be withheld if no DVT on bilateral leg ultrasound, no RV dysfunction, and no ongoing major thrombotic risk

• Provoked PE (reversible risk factor): minimum 3 months
• Unprovoked PE: at least 3-6 months; extended therapy considered based on bleeding risk
• Cancer-associated PE: indefinitely while cancer active

• UFH: protamine sulfate (near-complete reversal)
• LMWH: protamine (partial, ~50%)
• Apixaban/rivaroxaban: andexanet alfa (recombinant factor Xa decoy)
• Dabigatran: idarucizumab

Thrombolytic (Fibrinolytic) Therapy

• Clear indication: Hemodynamic instability (SBP <90 mmHg or >40 mmHg drop from baseline) - "massive PE"
• Controversial: Intermediate-high risk (submassive PE with RV dysfunction but stable BP)

• Alteplase (rtPA): 100 mg IV over 2 hours (preferred), or 0.6 mg/kg over 15 min for cardiac arrest
• Reteplase: 10 units IV x2 doses, 30 min apart
• Tenecteplase: single weight-based IV bolus

Advanced/Interventional Therapies

• Reasonable for Category E (high-risk, hemodynamically unstable)
• Can be considered for Category D1-D2 (intermediate-high risk)
• A Class 1 recommendation is given for Pulmonary Embolism Response Teams (PERTs) - multidisciplinary teams for complex cases

1. Catheter-directed thrombolysis (CDT) - local low-dose tPA infusion; lower bleeding risk than systemic thrombolysis; recent meta-analysis (2025) vs. mechanical thrombectomy showed comparable outcomes
2. Mechanical thrombectomy - catheter-based clot aspiration or fragmentation; growing evidence base
3. Surgical embolectomy - for patients with massive PE when thrombolysis is contraindicated or failed
4. IVC filter - reserved for PE with absolute contraindication to anticoagulation; not used instead of anticoagulation if anticoagulation is possible

Low-Risk PE: Outpatient Management

• Hemodynamically stable with normal vital signs
• No RV dysfunction on imaging or echocardiography
• No major comorbidities contraindicating home treatment
• Reliable access to anticoagulants and follow-up

Special Populations

PE in Pregnancy

• PE is the leading cause of maternal mortality in the US (~15% of maternal deaths)
• Risk is 5x higher than age-matched non-pregnant women
• Diagnosis complicated by: physiologic dyspnea of pregnancy, elevated baseline D-dimer, validated prediction rule limitations
• Imaging: V/Q preferred (lower fetal radiation); if CTPA used, halving the perfusion dose is standard
• Treatment: LMWH throughout pregnancy; DOACs and warfarin are contraindicated
• Murray & Nadel's Respiratory Medicine, p. 3029

PE with Cancer

• Highest recurrence and mortality risk
• Preferred anticoagulants: LMWH or DOACs (rivaroxaban, apixaban, edoxaban)

Chronic Complications

• Occurs in ~3-4% of patients after acute PE
• Persistent organized thrombus obstructs pulmonary vasculature -> progressive pulmonary hypertension
• Presents with exertional dyspnea, RV failure
• Diagnosed by V/Q scan + right heart catheterization
• Treatment: pulmonary endarterectomy (surgery of choice), balloon pulmonary angioplasty, or riociguat (medical therapy)

• Dyspnea, exercise intolerance, quality-of-life impairment persisting after acute PE
• Distinct from CTEPH (no pulmonary hypertension at rest)
• Managed with supervised rehabilitation

Key Recent Updates (2026 AHA/ACC Guideline)

1. New 5-category A-E classification replaces massive/submassive terminology
2. Class 1 recommendation for PERTs (Pulmonary Embolism Response Teams)
3. DOACs firmly established as first-line for most patients
4. Mechanical thrombectomy and CDT recognized as equivalent options for high-risk patients
5. This is the first-ever PE guideline from AHA/ACC, referenced as: Creager et al., J Am Coll Cardiol 2026

• Rosen's Emergency Medicine, 9e (Chapters 74)
• Murray & Nadel's Textbook of Respiratory Medicine (Chapters 18, 81)
• 2026 AHA/ACC/Multisociety Guideline for Acute PE - JACC 2026;87:1626-1710
• Recent meta-analysis: Mechanical thrombectomy vs CDT for PE, PMID 40269600