Pulmonary · PANCE / PANRE

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]
Diagnostic algorithm for suspected acute pulmonary embolism (ESC 2019 / CHEST 2021).

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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