What is the recommended approach to diagnose and treat pulmonary embolism, including risk assessment, imaging, anticoagulation, thrombolysis, IVC filter placement, and duration of therapy?

Pulmonary Embolism: Diagnosis and Treatment

Diagnosis

Base your diagnostic approach on clinical probability assessment using validated prediction rules, followed by D-dimer testing in low/intermediate probability patients, and CTPA as the definitive imaging modality. 1, 2

Initial Risk Stratification and Clinical Probability

• Immediately assess for hemodynamic instability (shock or systolic blood pressure <90 mmHg) to identify high-risk PE requiring urgent intervention 1, 2, 3
• Use either a three-level scheme (low, intermediate, high probability) or two-level scheme (PE unlikely vs. PE likely) for clinical probability assessment 1, 2
• In suspected high-risk PE with hemodynamic instability, perform bedside echocardiography or emergency CTPA depending on availability—do not delay treatment for imaging 1, 2, 3

D-Dimer Testing

• Measure D-dimer only in patients with low or intermediate clinical probability, or those classified as "PE unlikely"—use highly sensitive assays preferentially 1, 2
• Do NOT measure D-dimer in high clinical probability patients, as a normal result does not safely exclude PE 1
• If D-dimer is negative in low/intermediate probability patients, reject the diagnosis of PE without further testing (3-month thromboembolic risk <1%) 2, 4

Imaging Studies

• CTPA is the imaging test of first choice for hemodynamically stable patients with elevated D-dimer or high clinical probability 1, 2
• Accept the diagnosis of PE if CTPA shows a segmental or more proximal filling defect in patients with intermediate or high clinical probability 1
• Reject the diagnosis of PE without further testing if CTPA is normal in patients with low or intermediate clinical probability 1
• V/Q scintigraphy is a valid alternative when CTPA is contraindicated; reject PE if perfusion lung scan is normal 1, 2
• Do NOT perform CT venography as an adjunct to CTPA 1, 2
• Do NOT perform MRA to rule out PE 1, 2
• Accept the diagnosis of VTE if compression ultrasound shows proximal DVT in a patient with clinical suspicion of PE 1

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Treatment

High-Risk PE (Hemodynamically Unstable)

Administer systemic thrombolytic therapy immediately to all patients with high-risk PE and hypotension who lack high bleeding risk. 1, 3

Immediate Anticoagulation

• Initiate intravenous unfractionated heparin (UFH) without delay, including weight-adjusted bolus injection, even before imaging confirmation 1, 3
• UFH dosing: bolus of 5,000-10,000 units followed by continuous infusion of 400-600 units/kg/day (or 30,000-40,000 units/24 hours) 3
• Maintain aPTT at 1.5-2.5 times control value, measured 4-6 hours after initiation 3
• UFH is preferred over LMWH or fondaparinux in hemodynamically unstable patients 3

Thrombolytic Therapy

• Alteplase (rtPA) is the preferred agent: 0.6 mg/kg over 15 minutes (maximum 50 mg) or 100 mg over 2 hours 3
• Meta-analyses demonstrate significant mortality reduction in massive PE (OR 0.45; 95% CI 0.22-0.92) 3
• Major bleeding risk: 21.9% with thrombolysis vs. 11.9% with heparin alone in massive PE 3
• Administer rescue thrombolytic therapy if hemodynamic deterioration occurs despite anticoagulation 1

Alternative Interventions

• Surgical pulmonary embolectomy is indicated when thrombolysis is contraindicated or has failed to improve hemodynamic status within one hour 1, 3
• Catheter embolectomy or thrombus fragmentation may be considered if surgery is not immediately available 3
• ECMO may be considered in extreme cases 3

Hemodynamic Support

• Administer high-flow oxygen for hypoxemia correction 3
• Use vasopressor agents for hypotensive patients 3
• Consider dobutamine or dopamine in patients with low cardiac output and normal blood pressure 3
• Avoid aggressive fluid challenge—this worsens right ventricular failure 3
• Avoid diuretics and vasodilators as they may precipitate cardiovascular collapse 3

Intermediate- and Low-Risk PE (Hemodynamically Stable)

Initial Anticoagulation

• Initiate anticoagulation immediately in cases of high or intermediate clinical probability while diagnostic workup is in progress 1
• If parenteral anticoagulation is chosen, prefer LMWH or fondaparinux over UFH 1
• Do NOT routinely administer systemic thrombolysis as primary treatment in intermediate- or low-risk PE 1

Oral Anticoagulation Selection

• When initiating oral anticoagulation, prefer a NOAC (apixaban, dabigatran, edoxaban, or rivaroxaban) over vitamin K antagonists 1, 5
• As an alternative, administer a VKA overlapping with parenteral anticoagulation until INR reaches 2.5 (range 2.0-3.0) 1
• Do NOT use NOACs in patients with severe renal impairment or antiphospholipid antibody syndrome—use VKA indefinitely in these populations 1

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Duration of Anticoagulation

All patients with PE require therapeutic anticoagulation for a minimum of 3 months. 1, 3

Provoked PE (Transient Risk Factor)

• Discontinue anticoagulation after 3 months in patients with first PE secondary to a major transient/reversible risk factor 1

Unprovoked PE

• Consider extended anticoagulation beyond 3 months if bleeding risk is low or moderate 3
• Reassess at regular intervals: drug tolerance, adherence, hepatic/renal function, and bleeding risk 1

Recurrent VTE

• Continue oral anticoagulation indefinitely in patients with recurrent VTE (at least one previous PE or DVT episode) not related to a major transient/reversible risk factor 1

Special Populations

• Continue VKA indefinitely in patients with antiphospholipid antibody syndrome 1
• In pregnancy, administer therapeutic fixed-dose LMWH based on early pregnancy weight; do NOT use NOACs during pregnancy or lactation 1

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IVC Filter Placement

Do NOT routinely use inferior vena cava filters. 1

• IVC filters should be used only in patients at high risk of further emboli in whom anticoagulation is contraindicated, or with recurrent PE despite adequate anticoagulation 1

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Post-PE Care and Long-Term Follow-Up

• Routinely reevaluate patients at 3-6 months after acute PE to screen for chronic thromboembolic pulmonary hypertension (CTEPH) 3, 6
• Refer symptomatic patients with persistent perfusion defects on V/Q scan to a pulmonary hypertension/CTEPH expert center 3, 6
• Implement an integrated care model to ensure optimal transition from hospital to ambulatory care 3, 6
• All patients with confirmed CTEPH require lifelong anticoagulation with VKA (target INR 2.5, range 2.0-3.0) 6

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Critical Pitfalls to Avoid

• Never delay anticoagulation in high or intermediate probability cases while awaiting diagnostic confirmation 1
• Never measure D-dimer in high clinical probability patients—proceed directly to imaging 1
• Never use aggressive fluid resuscitation in massive PE—this exacerbates right ventricular failure 3
• Never delay referral to CTEPH expert centers once the diagnosis is suspected beyond 3 months post-PE 6
• Never use NOACs in severe renal impairment or antiphospholipid syndrome—VKA is mandatory 1