Pulmonary Embolism (PE) - Full Clinical Overview

Pathophysiology

1. Hypercoagulability (thrombophilia, cancer, oral contraceptives, immobility)
2. Venous stasis (prolonged immobilization, heart failure, post-surgical)
3. Venous injury/inflammation (trauma, surgery, IV catheters)

• Obstruction of the pulmonary vascular bed raises pulmonary vascular resistance (PVR)
• Acute pulmonary hypertension causes right ventricular (RV) pressure overload and dilation
• The dilated RV compresses the interventricular septum, reducing LV filling ("D-sign")
• Decreased LV cardiac output leads to systemic hypotension and ischemia
• In extreme cases, the thrombus can occlude the entire RV outflow system (as seen in the autopsy photo below), causing sudden cardiovascular collapse

Autopsy photograph showing massive PE completely occluding the right ventricular outflow system - Rosen's Emergency Medicine

• V/Q mismatch is the primary cause of hypoxemia
• Dead space ventilation increases (perfused segments lost)
• Reflex bronchoconstriction and atelectasis contribute
• Pulmonary infarction can occur in peripheral PE, producing pleuritic pain, hemoptysis, and fever

Risk Factors

Clinical Presentation

• Dyspnea - 75-80% of patients; can be constant, exertional, or vague ("can't take a full breath")
• Chest pain - second most common; can be pleuritic (sharp, worse with inspiration - seen in ~20%) or non-pleuritic (dull, aching)
• Cough, hemoptysis - with pulmonary infarction (peripheral PE)
• Unilateral leg swelling/pain - present in <30%, but relatively specific when combined with dyspnea
• Syncope - <5% of syncope patients have PE, but unexplained syncope with risk factors should prompt evaluation
• Low-grade fever - if high fever (>38.6°C/101.5°F), consider pneumonia instead

• Tachycardia (most common sign)
• Tachypnea, hypoxemia
• Hypotension/shock (massive PE)
• Loud P2, right-sided S3/S4, signs of RV failure (raised JVP, peripheral edema)
• PEA arrest is the most common ECG finding in PE-related cardiac arrest

Pearl: Approximately 25% of sudden cardiac deaths are attributed to PE.

Diagnosis & Workup

Step 1 - Estimate Pre-Test Probability (PTP)

• Low: <2 points | Moderate: 2-6 | High: >6

• Low: 0-3 | Intermediate: 4-10 | High: >10

Step 2 - Apply PERC Rule (if low gestalt PTP)

Age <50 | Pulse <100 | SaO2 >94% | No unilateral leg swelling | No hemoptysis | No recent trauma/surgery | No prior PE/DVT | No hormone use

Step 3 - D-Dimer

• Sensitivity 95-98%, specificity 40-55%
• Use in non-high PTP patients (Wells <6 or Geneva <5)
• Negative D-dimer effectively excludes PE (NPV 99-100%)
• Age-adjusted D-dimer threshold = age × 10 mcg/L (for patients >50 years) - increases specificity without sacrificing sensitivity

Step 4 - Imaging

• Visualizes emboli directly in pulmonary arteries
• Also shows RV dilation (ratio >0.9 signals intermediate/high risk)
• Preferred over V/Q in most patients

• Contrast allergy or renal impairment
• Pregnancy (lower fetal radiation vs. CTPA)
• Young women (lower breast radiation)

Ancillary Tests

Risk Stratification

Shock index >1 (HR > SBP) indicates hemodynamic compromise.

Management

Anticoagulation (cornerstone of treatment)

• Rivaroxaban: 15 mg BID x 21 days, then 20 mg daily
• Apixaban: 10 mg BID x 7 days, then 5 mg BID
• Dabigatran or Edoxaban: require 5-10 days of parenteral heparin first

• Use if thrombolysis or surgical intervention is planned
• UFH is preferred pre-thrombolysis (short half-life, reversible)
• LMWH (enoxaparin) preferred for cancer-associated PE

• Provoked PE (reversible risk factor): 3 months
• Unprovoked PE: minimum 3 months; consider extended if low bleeding risk
• Cancer-associated PE: long-term (DOAC or LMWH preferred)

Treatment by Risk Category

• DOAC anticoagulation
• Outpatient management appropriate if Hestia criteria negative or PESI class I-II
• Follow-up at 1-2 weeks

• Hospital admission (monitored bed); anticoagulation (DOAC or heparin)
• Thrombolysis reserved for clinical deterioration
• Activate PERT (PE Response Team) if available

• IV UFH immediately
• Systemic thrombolysis (alteplase 100 mg IV over 2 hours) - if no contraindications
• Surgical embolectomy - if thrombolysis contraindicated or failed
• Catheter-directed therapy (CDT) - alternative in intermediate-high risk or thrombolysis contraindications
• ECMO - as bridge to definitive therapy in refractory shock

Hemodynamic & Supportive Care

• Supplemental O2: target SpO2 >90%; avoid hypoxic pulmonary vasoconstriction
• Avoid aggressive fluid resuscitation - small boluses (250-500 mL) only; excessive fluids worsen RV dilation and LV compression
• Vasopressors: norepinephrine first-line for hypotension; dobutamine as adjunct (may worsen hypotension if used alone)
• Avoid intubation if possible - positive pressure ventilation increases intrathoracic pressure, reduces preload, and can precipitate hemodynamic collapse in severe PE. If intubation is unavoidable, optimize hemodynamics before induction.

IVC Filter

• Indicated when anticoagulation is absolutely contraindicated AND PE risk is high
• Retrievable filters preferred
• Does NOT replace anticoagulation - resume as soon as safe

Special Populations

Pregnancy

• Risk is ~5x that of non-pregnant women; peaks postpartum (especially post-C-section)
• Increased coagulation factors (V, VIII, X, vWF) and decreased protein S
• D-dimer is unreliable (normally elevated in pregnancy)
• Pregnancy-adapted YEARS algorithm may help guide testing
• Imaging: V/Q (lower breast radiation) vs. CTPA - both acceptable; halve the perfusion dose for V/Q
• Treatment: LMWH throughout pregnancy and postpartum (warfarin teratogenic; DOACs not approved)

Cancer

• LMWH (e.g., dalteparin) or DOACs (rivaroxaban, apixaban) preferred over warfarin
• Duration: indefinite while cancer is active
• Outpatient management increasingly supported - see recent meta-analysis (PMID 39603673)

Prognosis & Long-Term Complications

• 30-day mortality: <2% low-risk, up to 30-65% in massive PE with cardiac arrest
• Post-PE syndrome: dyspnea, exercise intolerance, decreased quality of life in ~50% at 1 year
• Chronic thromboembolic pulmonary hypertension (CTEPH): occurs in 0.5-5% of survivors; workup with V/Q scan at 3-6 months if persistent symptoms; definitive treatment is pulmonary endarterectomy
• Recurrence: ~10% at 1 year, ~30% at 10 years for unprovoked PE

PE Response Teams (PERT)