Pulmonary Embolism Diagnosis and Management

Clinical Assessment and Diagnostic Testing

• The European Society of Cardiology recommends applying validated clinical decision rules such as the Wells score or revised Geneva score to assess pretest probability of PE, with the American Society of Hematology suggesting their use before D-dimer testing 1, 2, 3
• An elevated D-dimer has high sensitivity but low specificity for PE and can be elevated in various conditions, including venous thromboembolism, sepsis, malignancy, recent trauma or surgery, acute myocardial infarction, pregnancy, and advanced age 1
• The American Society of Hematology advises against using a positive D-dimer alone to diagnose PE without confirmatory imaging 2
• Age-adjusted cutoffs should be used in older patients to avoid unnecessary testing, with a standard cutoff of 500 μg/L FEU and an age-adjusted cutoff for patients over 50 years (age × 10 μg/L), as recommended by the American College of Chest Physicians 2, 4

• Normal D-dimer ranges during pregnancy are:

  Trimester	Normal D-dimer Range
  First	0.11-0.40 μg/mL
  Second	0.14-0.75 μg/mL
  Third	0.16-1.3 μg/mL

  5

• COVID-19 and other viral infections can cause marked elevations in D-dimer levels, associated with disease severity and mortality, as reported by 6
• Liver disease can complicate the interpretation of D-dimer levels due to baseline coagulation abnormalities, as reported by 7
• Acute respiratory distress syndrome can be associated with elevated D-dimer levels, as reported by 8
• D-dimer levels are frequently elevated in COVID-19 patients, which can affect interpretation of results, and the American Society of Hematology guideline panel suggests using prophylactic-intensity anticoagulation for COVID-19 patients with acute illness, due to the hypercoagulable state with endotheliopathy 2, 9

Imaging and Diagnostic Timing

• For patients with suspected pulmonary embolism (PE), computed tomographic pulmonary angiography (CTPA) is the first-line imaging test, especially for those with elevated D-dimer and intermediate to high clinical probability of PE, as recommended by the European Society of Cardiology 1, 10
• If CTPA is contraindicated, consider compression ultrasonography (CUS) of lower extremities or V/Q scan, as suggested by the European Society of Cardiology 1, 10
• The British Thoracic Society recommends that imaging should ideally be performed within 24 hours in non-massive PE and within 1 hour in suspected massive PE 11

Management of Confirmed Pulmonary Embolism

• Immediately initiate intravenous unfractionated heparin (UFH) including weight-adjusted bolus for patients with confirmed PE, as recommended by the European Society of Cardiology 1
• Administer systemic thrombolytic therapy for patients with high-risk PE, as suggested by the European Society of Cardiology 1
• Consider surgical pulmonary embolectomy if thrombolysis is contraindicated or fails, according to the European Society of Cardiology 1
• For confirmed PE without hemodynamic instability, prefer low molecular weight heparin (LMWH) or fondaparinux over UFH, and consider transitioning to a direct oral anticoagulant (NOAC) as preferred option, as recommended by the European Society of Cardiology 1
• Standard prophylactic anticoagulation with low molecular weight heparin (LMWH) is recommended, with enoxaparin 40 mg daily as the preferred option, or unfractionated heparin (UFH) twice or thrice daily if LMWH is contraindicated, as recommended by the American College of Chest Physicians and the International Society on Thrombosis and Haemostasis 12, 13, 14
• In patients with confirmed PE, excessive oxygen administration can worsen hypercapnia 15

Anticoagulation Therapy

• Minimum 3 months for all patients with confirmed PE, as recommended by the European Society of Cardiology 1
• Consider discontinuing after 3 months if PE was provoked by a major transient/reversible risk factor, according to the European Society of Cardiology 1
• Continue indefinitely for unprovoked or recurrent VTE, as suggested by the European Society of Cardiology 1
• Reassess drug tolerance, adherence, hepatic and renal function, and bleeding risk at regular intervals for patients on extended anticoagulation, as recommended by the European Society of Cardiology 1
• Severe renal impairment is a contraindication for NOACs, as noted by the European Society of Cardiology 1
• Antiphospholipid antibody syndrome is a contraindication for NOACs, and VKA should be used instead, according to the European Society of Cardiology 1
• Pregnancy is a contraindication for NOACs, as recommended by the European Society of Cardiology 1
• Before escalating anticoagulation, ensure there are no contraindications, including no active bleeding, as recommended by the ISTH 14
• Platelet count should be greater than 25 × 10^9/L for non-bleeding patients before escalating anticoagulation, as recommended by the ISTH 14
• Bleeding risk assessment is crucial in patients receiving anticoagulation therapy, with maintenance of platelet count >25 × 10^9/L in non-bleeding patients and >50 × 10^9/L in bleeding patients, as well as keeping fibrinogen >1.5 g/L, as recommended by the International Society on Thrombosis and Haemostasis 14
• Anticoagulation should be adjusted based on renal function, weight, and bleeding risk, and modified based on extremes of body weight, severe thrombocytopenia, and deteriorating renal function, as recommended by the National Kidney Foundation and the Kidney Disease: Improving Global Outcomes (KDIGO) initiative 12, 16
• For critically ill COVID-19 patients, prophylactic-intensity over intermediate or therapeutic-intensity anticoagulation is recommended, as suggested by the American Society of Hematology and the World Journal of Emergency Surgery 9, 6