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2019 ESC Guidelines for Acute Pulmonary Embolism

Diagnosis and Management — Clinical Quick Reference

Published: European Heart Journal (2020) 41:543–603
Societies: ESC, ERS
DOI: 10.1093/eurheartj/ehz405
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What's New in 2019

Key Changes from Previous Guidelines

Clinical Presentation & Pre-Test Probability

Symptoms and Signs

Clinical findings are non-specific and overlap with many other conditions. PE should be suspected when:

Predisposing Factors

VTE risk varies with type of risk factor. Major trauma, surgery, lower-limb immobilization, and malignancy carry highest risk. Oral contraceptives and hormone replacement therapy significantly increase VTE risk in women.

Pearl: In ~40% of PE patients with symptoms, no predisposing factors are evident. Absence of risk factors does not exclude PE.

Diagnosis of PE

Diagnostic Approach Overview

The diagnostic workup relies on integration of clinical probability, D-dimer, and imaging tests (primarily CTPA). Structured diagnostic algorithms optimize both sensitivity (avoiding missed PE) and specificity (avoiding unnecessary treatment).

Clinical Probability Assessment

IA The diagnostic strategy should be based on clinical probability, assessed either by clinical judgment or by validated prediction rules (Wells score, Geneva score, or Hestia criteria).

Assessment of Clinical (Pre-Test) Probability

Clinical evaluation combined with predisposing factors determines baseline probability. This can be classified implicitly or using explicit rules, with the revised Geneva score and Wells score being most validated. Classification into low/intermediate/high probability helps guide subsequent testing.

Pre-Test Probability Implicit Clinical Judgment Revised Geneva (Points) Wells Score (Points)
Low PE unlikely 0–1 0–2
Intermediate PE possible 2–4 3–4
High PE likely ≥5 ≥5

Wells Score & Geneva Score for PE Probability

Revised Wells Score for PE

Criterion Points
Clinical signs of DVT (leg swelling, pain) 3
Alternative diagnosis less likely than PE 3
Heart rate >100 bpm 1.5
Immobilization ≥3 days or surgery in past 4 weeks 1.5
Previous DVT or PE 1.5
Haemoptysis 1
Malignancy (treatment ongoing or <6 months ago) 1

Interpretation: PE-unlikely: 0–4 points | PE-likely: ≥5 points

Revised Geneva Clinical Prediction Rule

Item Original Version (Points) Simplified Version (Points)
Previous PE or DVT 3 1
Heart rate 75–94 bpm 3 1
Heart rate ≥95 bpm 5 2
Surgery or fracture within past month 2 1
Haemoptysis 2 1
Active cancer 2 1
Unilateral lower-limb pain 3 1
Unilateral lower-limb oedema 4 1
Age ≥65 years 1 1

Interpretation — Original: Low 0–3 | Intermediate 4–10 | High ≥11

Interpretation — Simplified: Low 0–1 | Intermediate 2–4 | High ≥5

D-Dimer Testing & Interpretation

Clinical Role of D-Dimer

IA Plasma D-dimer measurement, preferably using highly sensitive assays, is recommended in outpatients/emergency department patients with low or intermediate clinical probability, or those PE-unlikely, to reduce need for unnecessary imaging.

Age-Adjusted D-Dimer Cutoffs

2aB As an alternative to fixed D-dimer cutoff, age-adjusted cutoff (age × 10 µg/L for patients aged >50 years) should be considered for excluding PE in patients with low or intermediate clinical probability, or those PE-unlikely.

Age-Adjusted D-Dimer Strategy:
  • Patients <50 years: Standard cutoff 500 µg/L
  • Patients ≥50 years: Cutoff = age × 10 µg/L (e.g., 60-year-old: 600 µg/L)
  • Improves negative predictive value in older patients without reducing sensitivity
  • D-dimer negative combined with low/intermediate pre-test probability excludes PE with ~98% safety

Point-of-Care D-Dimer Assays

IA In outpatient/emergency department settings, point-of-care D-dimer assays (on-site testing) may offer advantages over centralized laboratory testing, provided sensitivity and negative predictive value meet defined thresholds (≥85% and ≥98%, respectively).

Pitfall: D-dimer elevation is non-specific. High D-dimer alone (without clinical evidence) does not exclude PE and is not sufficient to withhold anticoagulation decision-making. Use in context of clinical probability.

Risk Stratification & Severity Assessment

Definition of Haemodynamic Instability

Haemodynamic instability defines acute high-risk PE requiring emergency intervention. Precise definition is critical for guiding management intensity.

Category Definition
Cardiac Arrest Need for cardiopulmonary resuscitation
Obstructive Shock Systolic BP <90 mmHg or vasopressors required to achieve BP ≥90 mmHg despite adequate filling status; end-organ hypoperfusion (altered mental status, cold/clammy skin, oliguria, increased serum lactate)
Persistent Hypotension Systolic BP <90 mmHg or BP drop ≥40 mmHg lasting >15 min not due to arrhythmia, hypovolaemia, or sepsis

Pulmonary Embolism Severity Index (PESI)

The PESI integrates clinical and baseline parameters to assess 30-day mortality risk in patients without haemodynamic instability. Two versions available: original (11 parameters) and simplified sPESI.

PESI Class Points Range 30-Day Mortality Risk
I (Low) ≤65 0–1% (95% CI 0.0–2.1%)
II 66–85 1.7–3.5%
III 86–105 3–7.1%
IV 106–125 4.0–11.4%
V (High) >125 10.0–24.5%

RV Dysfunction & Cardiac Biomarkers

2aB Assessment of RV function by imaging or laboratory biomarkers should be considered, even in presence of low PESI or negative sPESI.

Biomarkers of RV Dysfunction & Myocardial Injury:

Pearl: A normal RV on echocardiography or normal cardiac biomarkers support low-risk classification. However, their absence does not exclude RV involvement in early stages.

PE Severity Classification

Risk Category Haemodynamic Instability RV Dysfunction Myocardial Injury (Troponin/BNP)
High-Risk PE + (present) + or – + or –
Intermediate-High PE – (absent) + (present) + (elevated)
Intermediate-Low PE – (absent) + (present) – (normal)
Low-Risk PE – (absent) – (absent) – (normal)

Treatment in the Acute Phase

Overview of Acute PE Management

Acute treatment aims to (1) prevent haemodynamic decompensation and death, (2) prevent recurrent PE, and (3) facilitate recovery. Management intensity depends on risk stratification: high-risk PE requires emergency intervention, intermediate-risk requires close monitoring, and low-risk can often be managed with early discharge.

Oxygen Therapy & Ventilatory Support

IC Supplemental oxygen is indicated in patients with SaO₂ <90%. In severe hypoxaemia, high-flow oxygen, non-invasive ventilation (e.g., CPAP), or mechanical ventilation may be needed to correct ventilation-perfusion mismatch and maintain oxygenation.

Haemodynamic Support

In acute RV failure (high-risk PE), haemodynamic support strategies are tailored to the pathophysiology:

  • Fluid management: Cautious fluid loading only if central venous pressure is low (to avoid RV overdistension); Ringer's lactate or saline 0.5–1 L over 15–30 min
  • Vasopressors/inotropes: Norepinephrine (0.2–1.0 µg/kg/min) increases RV inotropy and systemic BP; dobutamine (2–20 µg/kg/min) improves RV contractility and lowers filling pressure but may cause hypotension
  • Mechanical circulatory support: Veno-arterial ECMO/extracorporeal life support for haemodynamically refractory cases

Anticoagulation Therapy

Initial Anticoagulation (Parenteral)

IC In patients with high or intermediate clinical probability of PE (or PE-unlikely with positive imaging), anticoagulation with UFH (unfractionated heparin) including weight-adjusted bolus, should be initiated without delay.

Parenteral Anticoagulation Regimens:

  • Unfractionated Heparin (UFH): Bolus 80 IU/kg IV over 2–5 min, followed by infusion 18 IU/kg/h (adjust by aPTT). Advantages: short half-life, reversible, easy dose adjustment
  • LMWH (Enoxaparin): 1 mg/kg subcutaneously BID; preferred for outpatient-eligible PE. No routine monitoring required
  • Fondaparinux: Weight-based single daily dosing (5 mg, 7.5 mg, or 10 mg) IV or subcutaneous; efficacy and safety comparable to LMWH

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs)

IA When anticoagulation is initiated in a patient with PE who is eligible for a NOAC (apixaban, dabigatran, edoxaban, or rivaroxaban), a NOAC is recommended in preference to a VKA, as first-line oral anticoagulant treatment.

NOAC Dosing for PE Treatment:

  • Apixaban: 10 mg BID × 7 days, then 5 mg BID long-term (or 2.5 mg BID if age ≥60, weight ≤60 kg, or Cr ≥1.5 mg/dL)
  • Dabigatran: UFH/LMWH bridging × 5–10 days, then 150 mg BID
  • Edoxaban: UFH/LMWH bridging × 5–10 days, then 60 mg daily (or 30 mg if body weight <60 kg, concomitant CYP3A4 inhibitor, or Cr >2.5–5 mg/dL)
  • Rivaroxaban: 15 mg BID × 21 days, then 20 mg daily (or 15 mg if Cr 30–49 mL/min)

Vitamin K Antagonists (Warfarin)

VKAs (e.g., warfarin) remain an option for patients who cannot use NOACs. Requires bridging with parenteral anticoagulant and INR monitoring (target INR 2–3).

Thrombolysis & Reperfusion Therapy

Systemic Thrombolysis

IB Systemic thrombolytic therapy is recommended for high-risk PE (confirmed by haemodynamic instability) to improve pulmonary perfusion and RV function, reduce mortality.

Thrombolytic Agent Dosing Regimen Key Notes
Alteplase (rtPA) 100 mg IV over 2 hours (standard); 50 mg over 1 h (accelerated) Most widely used; can be accelerated in high-risk situations
Tenecteplase Weight-based: 30–50 mg IV bolus over 10 sec Fibrin-specific; single-bolus administration more convenient
Streptokinase 250,000 IU loading dose 30 min, then 100,000 IU/h × 12–24 h Older agent; rarely used; requires aPTT monitoring
Urokinase 4400 IU/kg loading × 10 min, then 4400 IU/kg/h × 12–24 h Alternative if allergic to other agents

Contraindications to Fibrinolysis

Absolute: History of haemorrhagic stroke or stroke of unknown origin; ischaemic stroke in previous 6 months; central nervous system neoplasm; major trauma, surgery, or head injury in previous 3 weeks; active bleeding or bleeding diathesis

Relative: Transient ischaemic attack in previous 6 months; oral anticoagulation; pregnancy or first postpartum week; non-compressible puncture sites; traumatic resuscitation; refractory hypertension; advanced liver disease; active peptic ulcer

Catheter-Directed Thrombolysis

2aC Catheter-directed thrombolysis (CDT) or ultrasound-assisted thrombolysis may be considered as an alternative to systemic thrombolysis in intermediate-risk PE patients with contraindications to systemic thrombolysis or in selected cases of intermediate-risk PE.

Surgical Pulmonary Embolectomy

2aC Surgical pulmonary embolectomy should be considered as an alternative to rescue thrombolysis in high-risk PE in whom thrombolysis has failed or is contraindicated, and in selected intermediate-risk PE if expertise is available.

Chronic Treatment & Prevention of Recurrence

Duration of Anticoagulation

IA Therapeutic anticoagulation for ≥3 months is recommended for all patients with PE (regardless of provocation status).

Risk Category Estimated Recurrence Risk Duration Recommendation
Provoked PE (major) <3% per year 3 months of anticoagulation
Provoked PE (minor) 3–8% per year ≥3 months; consider extension based on clinical judgment
Unprovoked PE (first episode) ≥8% per year ≥3 months; extension recommended based on risk factors
Recurrent PE/VTE High Indefinite anticoagulation
PE with cancer High LMWH/DOAC or indefinite; reassess as cancer status evolves

Decision-Making for Extended Anticoagulation

2aA Extended oral anticoagulation of indefinite duration should be considered for patients presenting with a first episode of PE associated with a persistent risk factor (e.g., malignancy or antiphospholipid antibody syndrome).

2aC Extended oral anticoagulation of indefinite duration should be considered for patients with a first episode of PE without identifiable risk factor (unprovoked).

Pearl: The decision for extended anticoagulation after initial 3-month treatment should involve shared decision-making with the patient, considering bleeding risk (HAS-BLED, OBRI) against recurrence risk (PESI, D-dimer, imaging findings).

Pulmonary Embolism & Pregnancy

Epidemiology & Risk Factors

PE is a rare but potentially fatal complication of pregnancy, responsible for maternal death in high-income countries. VTE risk is increased 4–5-fold during pregnancy and peaks in postpartum period (up to 6 weeks post-delivery).

Diagnosis in Pregnancy

IB Formal diagnostic assessment with validated methods is recommended (PE is suspected during pregnancy).

Diagnostic Strategy:

Treatment in Pregnancy

IB A therapeutic fixed dose of LMWH based on early pregnancy body weight is recommended therapy for PE in the majority of pregnant women without haemodynamic instability.

Anticoagulation in Pregnancy:

  • LMWH: First-line; does not cross placenta; safe throughout pregnancy and lactation (dosing based on early pregnancy weight)
  • UFH: Can be used as alternative; used if renal impairment (CrCl <30 mL/min) or high risk of bleeding
  • Warfarin: Contraindicated in first trimester (teratogenic) and near delivery (fetal bleeding); use LMWH instead
  • NOACs: Contraindicated in pregnancy and lactation (insufficient safety data)

Thrombolysis & High-Risk PE in Pregnancy

2aC Thrombolysis or surgical pulmonary embolectomy should be considered for pregnant women with high-risk PE.

Postpartum Management: Anticoagulation should be continued for ≥6 weeks after delivery; longer duration (3 months) recommended if unprovoked PE.

PE in Patients with Cancer

Epidemiology & Risk Assessment

Patients with active cancer have significantly elevated VTE risk (3–7-fold higher than general population). Cancer-related VTE includes provoked PE/DVT and may be influenced by cancer type, stage, and treatment.

Anticoagulation in Cancer-Associated PE

2aA For patients with PE and cancer, weight-adjusted subcutaneous LMWH should be considered for the first 6 months over VKAs.

2aB Edoxaban should be considered as an alternative to weight-adjusted subcutaneous LMWH in patients without gastrointestinal cancer.

2aC Rivaroxaban should be considered as an alternative to weight-adjusted subcutaneous LMWH in patients without gastrointestinal cancer.

Duration of Treatment

2aB For patients with PE and cancer, extended anticoagulation (beyond the first 6 months) should be considered for an indefinite period or until cancer is cured.

Pearl: Cancer-related VTE often recurs despite anticoagulation. Indefinite anticoagulation is typically recommended unless cancer achieves complete remission with low risk of recurrence.

Do's & Don'ts in PE Management

Do:

  • Use integrated risk-adjusted diagnostic algorithms (Figures 4 & 5) to guide imaging decisions
  • Initiate anticoagulation promptly in high-risk PE without delay for imaging confirmation
  • Consider age-adjusted D-dimer cutoffs (age × 10 µg/L) in patients >50 years to improve diagnostic efficiency
  • Assess RV function by imaging or cardiac biomarkers in all PE patients, even with low clinical risk scores
  • Perform transthoracic echocardiography to exclude massive PE in haemodynamically unstable patients
  • Use CTPA as first-line imaging modality for PE diagnosis (high sensitivity and specificity)
  • Consider NOACs as first-line oral anticoagulants when eligibility criteria are met
  • Ensure shared decision-making regarding duration of anticoagulation after initial 3 months
  • Use LMWH as first-line anticoagulation in pregnant women; avoid warfarin in first trimester
  • Monitor for contraindications and drug interactions when initiating anticoagulation

Don't:

  • Do not delay anticoagulation in suspected PE pending diagnostic imaging if clinical risk is high
  • Do not use fixed high D-dimer threshold (≥500 µg/L) alone to diagnose PE without clinical correlation
  • Do not exclude PE diagnosis based on normal D-dimer if high clinical probability (use imaging instead)
  • Do not use CT pulmonary angiography as first-line imaging in all patients with low pretest probability (D-dimer more efficient)
  • Do not withhold systemic thrombolysis in high-risk PE solely due to relative contraindications if benefit exceeds risk
  • Do not routinely use heparin monitoring (aPTT) with LMWH or fondaparinux in non-obese patients with normal renal function
  • Do not assume normal RV on echocardiography excludes PE; imaging can be falsely negative early in disease
  • Do not use NOACs in pregnancy or postpartum women on breastfeeding (insufficient safety data)
  • Do not initiate indefinite anticoagulation in all unprovoked PE without discussing bleeding risk and individual preferences
  • Do not recommend IVC filter placement routinely in PE; reserve for haemodynamically unstable patients with contraindications to anticoagulation

Risk & Severity Calculators

Integrated clinical tools help quantify PE risk and guide management decisions. Use alongside clinical judgment.