What are the guidelines for the workup and treatment of a patient with suspected pulmonary embolism (PE)?

Pulmonary Embolism Workup and Guidelines

The diagnostic workup for suspected PE must be stratified by hemodynamic stability, with immediate bedside echocardiography or emergency CTPA for high-risk patients, while stable patients require clinical probability assessment followed by D-dimer testing (if low/intermediate probability) and definitive imaging with CTPA. 1

Initial Risk Stratification

All patients with suspected PE must be immediately stratified based on hemodynamic stability to identify high-risk cases. 1

• High-risk PE is defined by shock (systolic BP <90 mmHg), cardiac arrest, or persistent hypotension 1
• These patients require immediate consultant contact and aggressive management 2
• Hemodynamically stable patients can be further stratified into intermediate- and low-risk categories 1

Diagnostic Approach for High-Risk PE (Massive PE)

In suspected high-risk PE, perform bedside echocardiography or emergency CTPA immediately, depending on availability and clinical circumstances. 1

• Initiate intravenous anticoagulation with unfractionated heparin (UFH) without delay, including a weight-adjusted bolus injection, even before diagnostic confirmation 1
• Echocardiography will show indirect signs of acute pulmonary hypertension and right ventricular overload if PE is present 1
• In highly unstable patients, thrombolytic treatment may be initiated based on compatible echocardiographic findings alone 1
• Do not delay treatment for imaging in deteriorating patients 1, 2

Critical Pitfall

A normal lung scan or CTPA in suspected massive PE should prompt immediate search for alternative causes of shock (cardiogenic shock, tamponade, aortic dissection), as this essentially rules out PE 1

Diagnostic Approach for Hemodynamically Stable Patients

Base the diagnostic strategy on clinical probability assessment using either clinical judgment or a validated prediction rule. 1

Step 1: Clinical Probability Assessment

• Use validated clinical decision rules to categorize patients as low, intermediate, or high probability 1
• Initiate anticoagulation immediately in patients with high or intermediate clinical probability while diagnostic workup is in progress 1

Step 2: D-Dimer Testing (Selective Use)

Measure D-dimers in plasma, preferably with a highly sensitive assay, in outpatients/emergency department patients with low or intermediate clinical probability. 1

• Do not measure D-dimers in patients with high clinical probability, as a normal result does not safely exclude PE 1
• D-dimer <500 ng/mL combined with low clinical probability safely excludes PE without further testing 3
• Critical limitation: D-dimer has limited usefulness in hospitalized patients due to high prevalence of conditions causing elevation (infection, cancer, inflammation, recent surgery) 1

Step 3: Definitive Imaging

CTPA is the primary imaging modality for confirming or excluding PE in stable patients. 1

When to Use CTPA:

• First-line test in patients with elevated D-dimer 1
• First-line test in patients with high clinical probability (bypassing D-dimer) 1
• Accept the diagnosis of PE if CTPA shows a segmental or more proximal filling defect in a patient with intermediate or high clinical probability 1
• Reject the diagnosis of PE (without further testing) if CTPA is normal in a patient with low or intermediate clinical probability 1

Alternative Imaging Options:

Compression ultrasonography (CUS) of lower extremities:

• Accept the diagnosis of VTE if CUS shows a proximal DVT in a patient with clinical suspicion of PE—this is sufficient to warrant anticoagulation without further testing 1
• Consider CUS before CT in patients with contraindications to CT (renal failure, contrast allergy, pregnancy) 1
• CUS shows DVT in 30-50% of patients with PE 1

Ventilation-perfusion (V/Q) scintigraphy:

• Valid alternative when CTPA is contraindicated 1
• Preferred in younger patients and women to avoid radiation exposure and breast cancer risk 1
• Reject the diagnosis of PE if perfusion lung scan is normal 1
• V/Q scan is diagnostic (normal or high-probability) in approximately 30-50% of cases 1
• Higher diagnostic yield in patients with normal chest X-ray 1

Tests NOT Recommended:

• Do not perform CT venography as an adjunct to CTPA 1
• Do not perform MRA to rule out PE 1

Treatment Recommendations

Acute Phase Anticoagulation

For hemodynamically stable patients, prefer LMWH or fondaparinux over UFH when initiating parenteral anticoagulation. 1

When initiating oral anticoagulation in a patient eligible for treatment, prefer a NOAC (apixaban, dabigatran, edoxaban, or rivaroxaban) over warfarin. 1

NOAC Dosing Example (Apixaban):

• Treatment of PE: 10 mg orally twice daily for first 7 days, then 5 mg twice daily 4
• Reduction in risk of recurrence: 2.5 mg orally twice daily after at least 6 months of treatment 4

NOAC Contraindications:

• Do not use NOACs in patients with severe renal impairment or antiphospholipid antibody syndrome—use warfarin instead 1
• Do not use NOACs during pregnancy or lactation 1

Warfarin Alternative:

• Overlap with parenteral anticoagulation until INR reaches 2.5 (range 2.0-3.0) 1

Reperfusion Therapy

Administer systemic thrombolytic therapy to patients with high-risk PE. 1

• For massive PE with stable hemodynamics: alteplase 100 mg IV over 90 minutes 1
• For cardiac arrest: alteplase 50 mg IV bolus 1
• Surgical pulmonary embolectomy is indicated for high-risk PE when thrombolysis is contraindicated or has failed 1
• Do not routinely administer systemic thrombolysis as primary treatment in intermediate- or low-risk PE 1
• Administer rescue thrombolytic therapy to patients with hemodynamic deterioration despite anticoagulation 1

Duration of Anticoagulation

Administer therapeutic anticoagulation for at least 3 months to all patients with PE. 1

• Discontinue after 3 months in patients with first PE secondary to a major transient/reversible risk factor 1
• Continue indefinitely in patients with recurrent VTE not related to a major transient/reversible risk factor 1
• Continue indefinitely with warfarin (not NOAC) in patients with antiphospholipid antibody syndrome 1
• Consider extended therapy with apixaban 2.5 mg twice daily for recurrence prevention given the safety profile of DOACs 5

Special Populations

Pregnancy

Perform formal diagnostic assessment with validated methods if PE is suspected during pregnancy or postpartum. 1

• Administer therapeutic, fixed doses of LMWH based on early pregnancy weight in pregnant women without hemodynamic instability 1
• NOACs are absolutely contraindicated during pregnancy and lactation 1
• Do not insert spinal/epidural needle within 24 hours of last LMWH dose 1
• Do not administer LMWH within 4 hours of epidural catheter removal 1
• Obstetric consultation is mandatory 2

Hospitalized Patients

D-dimer testing has limited utility in hospitalized patients due to high false-positive rates from comorbidities 1

• Proceed directly to imaging in most hospitalized patients with suspected PE 1
• Clinical probability assessment is less discriminatory in postoperative patients 1

Post-PE Management

Routinely re-evaluate patients 3-6 months after acute PE. 1

• Implement integrated care model to ensure optimal transition from hospital to ambulatory care 1
• Refer symptomatic patients with mismatched perfusion defects on V/Q scan beyond 3 months to a pulmonary hypertension/CTEPH expert center 1
• Screen for chronic thromboembolic pulmonary hypertension using echocardiography, natriuretic peptides, and/or cardiopulmonary exercise testing 1, 5

Key Clinical Pitfalls

• Never delay anticoagulation in high or intermediate probability patients while awaiting diagnostic confirmation 1
• Never use D-dimer to exclude PE in high-probability patients or hospitalized patients 1
• Never discharge intermediate-risk patients without consultant review 2
• Do not routinely use inferior vena cava filters 1
• Subsegmental PE findings on CTPA require specialist consultation for management decisions 2