What is the diagnosis and management of pulmonary embolism?

Pulmonary Embolism: Diagnosis, Workup, and Management

Immediate Risk Stratification

Risk stratification based on hemodynamic stability is the critical first step that determines all subsequent management decisions. 1, 2, 3

• High-risk PE: Cardiogenic shock and/or persistent arterial hypotension—these patients require immediate systemic thrombolysis 2, 3
• Intermediate-risk PE: Hemodynamically stable with evidence of right ventricular dysfunction on imaging or biomarkers 2
• Low-risk PE: Hemodynamically stable without right ventricular dysfunction 2

Diagnostic Algorithm

Clinical Probability Assessment

• Assess clinical probability using validated criteria (Wells score or Geneva score) before ordering tests 3
• Do not measure D-dimer in high clinical probability patients—a normal result does not safely exclude PE in this population 3

D-dimer Testing

• Measure D-dimer only in patients with low or intermediate clinical probability 3
• A normal D-dimer excludes PE and no further testing is needed 4, 3
• In pregnancy, D-dimer has the same exclusion value despite physiologic elevation, though approximately 50% of women have normal levels at 20 weeks 4

Imaging

• CT pulmonary angiography (CTPA) is the initial lung imaging modality of choice for non-massive PE 3
• If CTPA is negative but clinical suspicion remains high, perform lower limb compression ultrasonography—positive DVT warrants anticoagulation without thoracic imaging 4
• In pregnancy, CTPA delivers lower fetal radiation than perfusion scanning in first/second trimester and can be performed safely (all tests deliver <50 mSv, well below the 50,000 mGy danger threshold) 4

Acute Management by Risk Category

High-Risk PE (Hemodynamically Unstable)

Systemic thrombolytic therapy is first-line treatment for high-risk PE unless contraindicated. 1, 3

Immediate Actions (Do Not Delay):

• Start intravenous unfractionated heparin immediately: 5,000-10,000 unit bolus, then 400-600 units/kg/day continuous infusion 2, 3
• Administer oxygen to correct hypoxemia 1, 3
• Correct systemic hypotension to prevent right ventricular failure progression 1, 3

Thrombolysis Protocol:

• Absolute contraindications: Hemorrhagic stroke or stroke of unknown origin (any time), ischemic stroke within 6 months, CNS damage/neoplasms, recent major trauma/surgery/head injury, GI bleeding within last month, known active bleeding 2
• Relative contraindications: TIA within 6 months, oral anticoagulant therapy, pregnancy or within 1 week postpartum, non-compressible punctures, traumatic resuscitation, refractory hypertension, advanced liver disease, infective endocarditis, active peptic ulcer 2

If Thrombolysis Fails or Is Contraindicated:

• Surgical pulmonary embolectomy is the recommended alternative 1, 2, 3
• Catheter embolectomy or fragmentation may be considered when surgery is not feasible 2

Intermediate-Risk PE

• Initiate anticoagulation without delay 1
• Prefer low-molecular-weight heparin (LMWH) or fondaparinux over unfractionated heparin 1, 2
• Consider thrombolysis only in selected patients with clinical deterioration 1
• Do not routinely administer systemic thrombolysis in intermediate-risk PE 3

Low-Risk PE

• Initiate LMWH or fondaparinux 2, 3
• Transition to oral anticoagulation as outlined below 2, 3

Anticoagulation Strategy

Initial Parenteral Anticoagulation

For hemodynamically stable patients, prefer LMWH or fondaparinux over unfractionated heparin. 2, 3

• Unfractionated heparin is reserved for high-risk PE or when rapid reversal may be needed 2, 3
• Continue parenteral anticoagulation for at least 5 days when using vitamin K antagonists 3

Oral Anticoagulation

Non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists for most patients. 2, 3

• Preferred NOACs: Apixaban, dabigatran, edoxaban, or rivaroxaban 2, 3, 5
• Do not use NOACs in patients with severe renal impairment or antiphospholipid antibody syndrome 3
• If using vitamin K antagonists: overlap with parenteral anticoagulation until INR reaches 2.5 (range 2.0-3.0) 3

Duration of Anticoagulation

All patients require at least 3 months of therapeutic anticoagulation. 2, 3

After 3 Months, Decision Algorithm:

• Discontinue anticoagulation: First PE secondary to major transient risk factor (e.g., surgery, trauma) 3
• Consider extended anticoagulation:
  • No identifiable risk factor (unprovoked PE) 2
  • Persistent risk factor other than antiphospholipid antibody syndrome 2
  • Minor transient/reversible risk factor 2
• Indefinite anticoagulation: Recurrent VTE not related to major transient risk factor 3

Special Populations

Pregnancy

• Normal D-dimer has same exclusion value as non-pregnant patients 4
• Perform lower limb ultrasound before thoracic imaging if D-dimer elevated 4
• CTPA is safe in pregnancy (fetal radiation <50 mSv) 4
• Perfusion lung scintigraphy is also reasonable with 75% diagnostic yield 4

IVC Filters

• Do not routinely use IVC filters in patients with PE 4, 3
• Consider only when absolute contraindications to anticoagulation exist with high VTE recurrence risk (e.g., immediately post-neurosurgery, major surgery) 4
• Use retrievable filters and remove as soon as anticoagulation is safe 4

Follow-Up Care

Routinely re-evaluate all patients 3-6 months after acute PE. 1, 2, 3

• Implement integrated care model for optimal hospital-to-ambulatory transition 1, 2, 3
• Refer to pulmonary hypertension expert center if persistent symptoms or mismatched perfusion defects beyond 3 months 1
• Screen for chronic thromboembolic pulmonary hypertension, which carries significant morbidity and mortality 6

Critical Pitfalls to Avoid

• Never delay anticoagulation while awaiting diagnostic confirmation in intermediate or high clinical probability patients 3
• Never measure D-dimer in high clinical probability patients 3
• Never routinely use systemic thrombolysis in intermediate- or low-risk PE 3
• Never use NOACs in severe renal impairment or antiphospholipid antibody syndrome 3
• In pregnancy, do not withhold diagnostic imaging due to radiation concerns—missing PE is more dangerous than radiation exposure 4
• Recent evidence shows alteplase has lower major bleeding risk (10.9%) compared to tenecteplase (31.1%) and catheter-directed thrombolysis (21.4%) 7