Pulmonary Embolism (PE)
Obstruction of pulmonary arterial circulation, usually by deep venous thrombus.
Also known as: PE, pulmonary embolism, VTE, venous thromboembolism, saddle embolus, massive PE, submassive PE
Overview
Acute occlusion of one or more pulmonary arteries by thromboembolus, most commonly originating from a lower-extremity deep vein thrombosis. Severity ranges from incidental subsegmental PE to massive PE with hemodynamic collapse.
Epidemiology
VTE affects ~1-2 per 1000 adults annually. PE causes ~100,000 US deaths/year. Recurrence rate ~30% over 10 years without secondary prevention.
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Risk factors
- Virchow triad: venous stasis, endothelial injury, hypercoagulability
- Recent surgery (especially orthopedic, abdominopelvic, neurosurgery), trauma, immobilization
- Malignancy (especially pancreatic, gastric, brain, lung, hematologic)
- Pregnancy/postpartum, estrogen therapy (OCPs, HRT)
- Prior VTE, family history
- Inherited thrombophilias: factor V Leiden, prothrombin G20210A, antithrombin/protein C/S deficiency, antiphospholipid syndrome
- Obesity, advanced age, smoking, long travel (>4 h)
Pathophysiology
Thromboembolus lodges in pulmonary arteries → mechanical obstruction + neurohumoral vasoconstriction → increased pulmonary vascular resistance. Right ventricular afterload rises; severe RV strain can cause hypotension, shock, and death. V/Q mismatch (perfusion of unventilated alveoli initially, then bronchoconstriction) → hypoxemia.
Clinical presentation
Symptoms
- Sudden dyspnea (most common), pleuritic chest pain, cough
- Hemoptysis (rare; suggests pulmonary infarction)
- Syncope or near-syncope (suggests hemodynamically significant PE)
- Unilateral leg pain or swelling (concurrent DVT)
Signs / physical exam
- Tachypnea, tachycardia, hypoxia
- Hypotension and shock (massive PE)
- Elevated JVP, accentuated P2, right-sided S3, parasternal heave (RV strain)
- Calf or thigh tenderness, swelling, Homan sign (low sensitivity/specificity)
Classic findings
Hampton hump (peripheral wedge-shaped opacity), Westermark sign (focal oligemia), Fleischner sign (enlarged pulmonary artery) on CXR — all insensitive.
Differential diagnosis
- Acute coronary syndrome — Substernal pressure rather than pleuritic; ECG ischemic changes; troponin rise pattern; coronary anatomy on cath
- Pneumonia — Fever, productive cough, lobar consolidation on CXR; positive cultures
- Pneumothorax — Unilateral absent breath sounds, hyperresonance; CXR diagnostic
- Aortic dissection — Tearing pain radiating to back, BP differential, widened mediastinum on CXR/CT
- Heart failure exacerbation — Orthopnea, PND, elevated BNP, bilateral edema; echocardiogram
- Musculoskeletal chest pain — Reproducible with palpation; normal vitals and oxygenation
- Pericarditis/tamponade — Pleuritic pain improved leaning forward, diffuse ST elevation; pericardial effusion on echo
- Anxiety/hyperventilation — Diagnosis of exclusion; normal ABG except respiratory alkalosis; no risk factors
Diagnostic workup
Diagnostic criteria
Confirmed PE on imaging. Use validated clinical decision rules: Wells score (low <2, moderate 2-6, high >6) or revised Geneva. PERC rule (8 criteria) can exclude PE in low-probability patients (<15%) without further testing.
Labs
- D-dimer — sensitive but not specific; useful to rule out PE in low-probability patients (age-adjusted threshold: age × 10 ng/mL in patients >50)
- Troponin and BNP — elevated in RV strain, prognostic (submassive PE)
- ABG — hypoxemia, hypocapnia, widened A-a gradient (but normal in up to 20%)
- CBC, BMP, INR/PTT before anticoagulation
- Thrombophilia workup if unprovoked and young; defer testing until after acute treatment
Imaging
- CT pulmonary angiography (CTPA) — gold standard if no contraindication
- V/Q scan — alternative if CTPA contraindicated (renal failure, contrast allergy, pregnancy with low CXR yield)
- Lower extremity Doppler — supportive when PE imaging contraindicated
- Echocardiogram — RV dilation/dysfunction, McConnell sign (akinesia of RV mid-free wall with sparing of apex), pulmonary hypertension; useful for risk stratification not diagnosis
- CXR — usually normal or nonspecific; helps exclude alternatives
- 12-lead ECG — sinus tachycardia (most common), S1Q3T3 (classic but uncommon), RBBB, T-wave inversion V1-V4
Diagnostic algorithm
flowchart TD
A[Suspected PE] --> B{Hemodynamically<br/>unstable?}
B -->|Yes| C[Bedside echo<br/>RV strain?]
C -->|Yes| D[Systemic thrombolysis<br/>or embolectomy]
B -->|No| E[Wells / Geneva<br/>pretest probability]
E -->|Low + PERC negative| F[PE excluded]
E -->|Low/Moderate| G[D-dimer<br/>age-adjusted]
G -->|Negative| F
G -->|Positive| H[CTPA]
E -->|High| H
H -->|Negative| I[Consider alternative dx]
H -->|Positive| J[Anticoagulation<br/>DOAC preferred]Treatment
First-line
- Anticoagulation while awaiting imaging if high clinical suspicion and low bleeding risk
- Hemodynamically stable PE: direct oral anticoagulant (DOAC) preferred — apixaban (10 mg BID × 7 d, then 5 mg BID) or rivaroxaban (15 mg BID × 21 d, then 20 mg daily) — no parenteral lead-in
- Alternative: dabigatran or edoxaban (require initial parenteral lead-in × 5-10 days)
- Parenteral options: low-molecular-weight heparin (enoxaparin 1 mg/kg q12h) or unfractionated heparin (preferred if thrombolysis or surgery anticipated, renal failure, hemodynamic instability)
- Hemodynamically unstable (massive PE — SBP <90 or vasopressor-dependent): systemic thrombolysis with alteplase 100 mg IV over 2 h
- Catheter-directed thrombolysis or surgical/catheter embolectomy if contraindications to systemic thrombolysis or as alternative
- Pregnancy: LMWH (does not cross placenta); avoid warfarin and DOACs
Second-line / adjunct
- Duration: ≥3 months for provoked PE (transient risk factor); indefinite for unprovoked, recurrent, active malignancy, or persistent risk factors
- Cancer-associated VTE: DOACs (apixaban, edoxaban, rivaroxaban) — non-inferior to LMWH (CARAVAGGIO, Hokusai-VTE Cancer trials); LMWH still preferred for GI/GU malignancies due to bleeding risk
- IVC filter only if absolute contraindication to anticoagulation; remove when anticoagulation can resume
- Submassive PE (RV dysfunction or troponin elevation, but no shock): risk-stratify; consider half-dose tPA or catheter-directed thrombolysis in select patients (PEITHO: thrombolysis reduced hemodynamic decompensation but NOT mortality, with increased major bleeding and stroke)
- Outpatient management of low-risk PE (sPESI = 0, normal RV) is appropriate
Complications
- Cardiogenic shock, cardiac arrest (PEA most common arrest rhythm)
- Chronic thromboembolic pulmonary hypertension (CTEPH) — occurs in ~3% post-PE; treat with pulmonary endarterectomy (curative) or riociguat
- Recurrence (~30% over 10 years without secondary prevention)
- Bleeding from anticoagulation, including intracranial hemorrhage
- Heparin-induced thrombocytopenia (HIT) with platelet drop >50%
PANCE pearls
- PERC rule rules out PE without D-dimer in low-pretest-probability patients meeting all 8 criteria: age <50, HR <100, SpO2 >94%, no hemoptysis, no estrogen, no prior VTE, no recent surgery/trauma, no unilateral leg swelling.
- Massive PE = hemodynamic instability; submassive = stable BP but RV dysfunction or troponin+; low-risk = stable, no RV strain. Risk-stratification (sPESI, PESI) drives disposition.
- ECG findings of severe PE: S1Q3T3 (S in I, Q and inverted T in III), new RBBB, T-wave inversions in anterior leads. Sinus tach remains the most common ECG finding.
- Wells criteria + age-adjusted D-dimer (age × 10 ng/mL if >50) safely reduce CTPA imaging in low-probability patients (ADJUST-PE).
- DOACs are first-line for most non-pregnant patients with normal renal function; apixaban and rivaroxaban require no parenteral lead-in.
References
- CHEST 2021 — Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report (Stevens et al., Chest 2021)
- ESC 2019 — 2019 ESC Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism (Konstantinides et al., Eur Heart J 2020)
- PEITHO Trial — Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism (Meyer et al., NEJM 2014)
- ADJUST-PE — Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism (Righini et al., JAMA 2014)
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