How should pulmonary thromboembolism be assessed and managed, including risk stratification, anticoagulation, thrombolysis, and follow‑up?

Management of Pulmonary Thromboembolism

Immediately assess hemodynamic status to identify high-risk PE requiring urgent thrombolysis, then risk-stratify stable patients using validated scores combined with imaging and biomarkers to guide anticoagulation strategy and duration. 1, 2

Initial Assessment and Risk Stratification

Step 1: Hemodynamic Assessment

• High-risk (massive) PE is defined by shock or persistent hypotension (systolic BP <90 mmHg for ≥15 minutes, or pressure drop ≥40 mmHg not caused by arrhythmia, hypovolemia, or sepsis), accounting for ~5% of cases with 30% mortality. 1, 3
• Look specifically for: heart rate >110 bpm, need for vasopressors, altered mental status, cold extremities, oliguria, and elevated lactate. 1
• Initiate IV unfractionated heparin immediately with weight-adjusted bolus (80 units/kg or 5,000-10,000 units) even before imaging confirmation when high-risk PE is suspected. 1, 2

Step 2: Risk-Stratify Normotensive Patients

• Use Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI) to separate intermediate- from low-risk patients. 1, 3
• sPESI assigns 1 point each for: age >80 years, active cancer, chronic cardiopulmonary disease, heart rate ≥110/min, oxygen saturation <90% on room air. 1, 3
• Low-risk PE: sPESI = 0 or PESI class I-II, with <1% 30-day mortality. 1, 3
• Intermediate-risk PE: sPESI ≥1 or PESI class III-V in hemodynamically stable patients, with 3-15% mortality. 1, 3

Step 3: Assess Right Ventricular Dysfunction and Biomarkers

• Measure RV/LV ratio on CTPA (>0.9 indicates dysfunction) or perform echocardiography to assess RV dilatation and function. 1, 3
• Measure troponin and BNP/NT-proBNP; elevated levels indicate myocardial injury and higher risk. 1, 3
• Intermediate-high risk: both RV dysfunction on imaging AND elevated biomarkers present. 3
• Intermediate-low risk: either RV dysfunction OR elevated biomarkers, but not both. 3

Treatment of High-Risk PE

Primary Reperfusion Therapy

• Administer systemic thrombolysis immediately to all high-risk patients without high bleeding risk—this is the only Class I, Level A recommendation that reduces mortality. 1, 2, 4
• Alteplase dosing: 100 mg IV over 2 hours, or 0.6 mg/kg over 15 minutes (maximum 50 mg) in cardiac arrest. 2, 4
• Do not delay thrombolysis for traditional contraindications in life-threatening PE; mortality benefit outweighs bleeding risk. 2
• Meta-analyses show thrombolysis reduces mortality/recurrence (OR 0.45; 95% CI 0.22-0.92) but increases major bleeding (21.9% vs 11.9% with heparin alone). 2

Alternative Reperfusion When Thrombolysis Fails or Is Contraindicated

• Surgical pulmonary embolectomy is the preferred alternative when thrombolysis is absolutely contraindicated or fails to improve hemodynamics within 1 hour. 1, 2, 4
• Catheter-directed embolectomy or thrombus fragmentation may be considered when surgery is unavailable, though evidence is limited. 2, 4, 5
• VA-ECMO can bridge patients with profound hemodynamic collapse to definitive intervention. 4

Hemodynamic Support

• Use vasopressors (norepinephrine, vasopressin) for hypotension. 1, 4
• Use inotropes (dobutamine, dopamine) for low cardiac output with normal BP. 1, 4
• Avoid aggressive fluid boluses (>500 mL)—this worsens RV failure by increasing afterload. 1, 4, 3
• Provide high-flow oxygen to correct hypoxemia (target SpO₂ >90%). 1

Treatment of Intermediate- and Low-Risk PE

Anticoagulation Strategy

• Prefer LMWH or fondaparinux over UFH for parenteral anticoagulation in hemodynamically stable patients. 1, 2, 4
• Enoxaparin dosing: 1 mg/kg subcutaneously every 12 hours (or 1.5 mg/kg once daily for inpatients). 4
• Reserve UFH for severe renal impairment (CrCl <30 mL/min), severe obesity, or when reperfusion therapy is being considered; target aPTT 1.5-2.5× control. 1, 2, 4
• Initiate anticoagulation immediately in patients with high or intermediate clinical probability while diagnostic workup proceeds. 1, 2

Thrombolysis in Intermediate-Risk PE

• Do not routinely use systemic thrombolysis in intermediate- or low-risk PE. 1, 2, 4
• PEITHO trial showed tenecteplase reduced death/decompensation (2.6% vs 5.6%) but did not lower mortality and doubled major bleeding. 4
• Reserve rescue thrombolysis only for patients who deteriorate hemodynamically despite adequate anticoagulation. 1, 2, 4

Oral Anticoagulation and Duration

Choice of Oral Agent

• Prefer a NOAC (apixaban, rivaroxaban, edoxaban, dabigatran) over warfarin for all eligible patients. 1, 2, 4
• NOAC contraindications: CrCl <25-30 mL/min, antiphospholipid antibody syndrome, pregnancy/lactation, edoxaban when CrCl >95 mL/min. 1, 2, 4
• Warfarin requires overlap with parenteral anticoagulation for ≥5 days and until INR 2.0-3.0 (target 2.5) on two consecutive measurements ≥24 hours apart. 1, 2, 4

Duration of Anticoagulation

• All patients require minimum 3 months of therapeutic anticoagulation. 1, 2, 4
• Provoked PE (major transient risk factor: surgery, trauma, immobilization): stop after 3 months. 1, 2, 4
• Unprovoked PE: continue indefinitely if bleeding risk is low-to-moderate; annual recurrence risk exceeds 5%. 1, 2, 4
• Recurrent VTE (≥1 prior episode): continue indefinitely. 1, 2, 4
• Antiphospholipid antibody syndrome: continue VKA indefinitely; NOACs are contraindicated. 1, 2, 4
• Active cancer: continue anticoagulation indefinitely with LMWH or NOAC (edoxaban or rivaroxaban preferred). 4

Monitoring During Extended Therapy

• Reassess drug tolerance, adherence, hepatic/renal function, bleeding risk (including NSAID use), and resolution of provoking factors at 3-6 months and then annually. 1, 2, 4

Outpatient Management of Low-Risk PE

Patient Selection

• PESI class I-II, sPESI = 0, or meeting Hestia criteria should be considered for outpatient management. 1
• Exclusion criteria: hemodynamic instability (HR >110, SBP <100), SpO₂ <90% on air, active bleeding or high bleeding risk, severe pain requiring opiates, CKD stage 4-5 (eGFR <30), severe liver disease, social barriers (no home support, no phone, compliance concerns). 1
• Do not routinely measure RV/LV ratio or biomarkers for low-risk outpatient selection, but if RV dilatation is incidentally found on CT, measure biomarkers—elevated values mandate inpatient admission. 1

Special Situations

Inferior Vena Cava Filters

• Do not routinely place IVC filters. 1, 2, 4
• Retrievable filters are reserved only for: absolute contraindication to anticoagulation, anticoagulation cannot be started within 1 month of symptomatic VTE, or recurrent PE despite therapeutic anticoagulation. 4
• Schedule frequent follow-up to reassess eligibility for anticoagulation and plan filter removal. 4

Pregnancy

• Therapeutic fixed-dose LMWH based on early-pregnancy weight is the anticoagulant of choice; NOACs are absolutely contraindicated. 1, 2
• Delay spinal/epidural procedures ≥24 hours after last LMWH dose and withhold LMWH ≥4 hours after catheter removal. 2
• Reserve thrombolysis for life-threatening hemodynamic instability due to high maternal hemorrhage risk. 4

Incidental and Subsegmental PE

• Anticoagulate incidental/subsegmental PE unless contraindicated; recurrence risk equals symptomatic PE. 4
• Outpatient management is appropriate for low-risk incidental PE. 4

Follow-Up and Chronic Complications

• Re-evaluate all patients at 3-6 months after acute PE to assess for chronic complications and determine need for continued anticoagulation. 2, 4
• Refer patients with persistent dyspnea and mismatched perfusion defects on V/Q scan beyond 3 months to a pulmonary hypertension/CTEPH expert center. 2, 4
• Implement an integrated care model to ensure optimal transition from hospital to ambulatory care. 2

Critical Pitfalls to Avoid

• Never delay anticoagulation in high- or intermediate-probability PE while awaiting imaging confirmation. 1, 2, 4
• Never measure D-dimer in patients with high clinical probability; proceed directly to CTPA. 1, 2
• Never perform CT venography as an adjunct to CTPA; it adds radiation without diagnostic benefit. 1, 2
• Never use NOACs in severe renal impairment (CrCl <25-30 mL/min) or antiphospholipid syndrome; warfarin is mandatory. 1, 2, 4
• Never withhold thrombolysis in massive PE solely because of relative contraindications; mortality risk from untreated PE exceeds bleeding risk. 2
• Never use catheter-directed thrombolysis routinely in hemodynamically stable patients; favorable risk-benefit profile has not been demonstrated. 4, 5