What are the recommended prevention and management strategies for pulmonary embolism in adults, including acute anticoagulation, thrombolysis for massive PE, prophylaxis regimens, and special considerations for pregnancy, active cancer, and renal impairment?

Pulmonary Embolism: Prevention and Management

Immediate Risk Stratification and Initial Anticoagulation

For hemodynamically unstable PE (systolic BP <90 mmHg or shock), administer systemic thrombolysis with alteplase 100 mg over 2 hours immediately, concurrent with unfractionated heparin. 1, 2

High-Risk (Massive) PE

• Start unfractionated heparin (UFH) with an 80 units/kg IV bolus followed by 18 units/kg/hour continuous infusion, targeting aPTT 1.5-2.5 times control 2, 3
• Administer thrombolytic therapy without delay; if contraindicated or failed, proceed to surgical pulmonary embolectomy 1
• UFH is mandatory in this setting because it can be rapidly reversed if bleeding complications arise during thrombolysis 3

Intermediate-Risk PE (Hemodynamically Stable with RV Dysfunction)

• Do not routinely administer thrombolysis—this is a Class III recommendation reserved strictly for high-risk PE 1, 4
• Initiate LMWH or fondaparinux over UFH in hemodynamically stable patients 1
• Reserve rescue thrombolysis only if hemodynamic deterioration develops despite adequate anticoagulation 1, 4, 3
• Monitor closely for signs requiring escalation: persistent hypotension, new vasopressor requirement, worsening hypoxemia, or rising lactate 3

Low-Risk PE

• Start LMWH or fondaparinux subcutaneously at weight-adjusted doses 1, 5
• Selected low-risk patients without serious comorbidity may be candidates for outpatient treatment 5

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Oral Anticoagulation Selection

When initiating oral anticoagulation in PE patients eligible for NOACs, prefer a NOAC (apixaban, rivaroxaban, dabigatran, or edoxaban) over vitamin K antagonists. 1, 2

Single-Drug NOAC Regimens (No Parenteral Lead-In Required)

• Rivaroxaban: 15 mg orally twice daily for 21 days, then 20 mg once daily 2
• Apixaban: 10 mg orally twice daily for 7 days, then 5 mg twice daily 2
• These regimens eliminate the need for initial LMWH and shorten hospital length of stay (45% discharged ≤5 days vs 33% with enoxaparin/warfarin, p<0.001) 2

NOACs Requiring Parenteral Lead-In

• Dabigatran and edoxaban: Administer therapeutic LMWH for at least 5 days before switching to oral agent 2

Vitamin K Antagonist (VKA) Alternative

• Overlap parenteral anticoagulation (LMWH or UFH) with warfarin for minimum 5 days and until INR ≥2.0 on two consecutive days 1, 2
• Target INR 2.0-3.0 throughout therapy 1, 2
• Initiate warfarin at 10 mg daily in younger adults (<60 years) and ≤5 mg daily in older adults 2

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Absolute Contraindications to NOACs

Do not use NOACs in the following populations—switch to alternative anticoagulation: 1, 2

• Severe renal impairment (CrCl <30 mL/min for rivaroxaban; <15 mL/min for apixaban)
• Antiphospholipid antibody syndrome (especially triple-positive)—use VKA with target INR 2.0-3.0 indefinitely
• Pregnancy or lactation
• Concurrent strong P-glycoprotein and CYP3A4 inhibitors (e.g., ritonavir, ketoconazole)

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Duration of Anticoagulation

All patients with PE require a minimum of 3 months of therapeutic anticoagulation. 1, 2

Provoked PE (Major Transient Risk Factor)

• Discontinue anticoagulation after 3 months if PE was secondary to surgery, trauma, or prolonged immobilization 1, 2

Unprovoked PE or Recurrent VTE

• Continue anticoagulation indefinitely after balancing individual bleeding risk 1, 2
• After 6 months of full-dose therapy, consider dose reduction to apixaban 2.5 mg twice daily to lower bleeding risk while preserving efficacy 2

Antiphospholipid Antibody Syndrome

• Continue VKA indefinitely; NOACs are contraindicated 1

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Special Populations

Active Cancer

• Prefer extended monotherapy with therapeutic LMWH (minimum 6 months) over warfarin or NOACs 2, 4
• Continue LMWH as long as cancer is active, as cancer-associated thrombosis carries threefold higher recurrence risk 2, 4
• Options include dalteparin or enoxaparin at therapeutic weight-adjusted doses 4

Pregnancy

• Use therapeutic fixed-dose LMWH based on early pregnancy weight throughout gestation 1, 2
• Continue LMWH for at least 6 weeks postpartum or 3 months from index PE, whichever is longer 2
• 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
• Warfarin may be initiated postpartum and does not preclude breastfeeding 2

Severe Renal Impairment

• Use UFH with aPTT monitoring (target 1.5-2.5 times control) rather than LMWH or fondaparinux, which accumulate and increase bleeding risk 4, 3
• If CrCl 30-50 mL/min, dose-adjusted LMWH may be considered after initial UFH stabilization with careful monitoring 3

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Interventions NOT Recommended

The following are Class III recommendations—do not perform routinely: 1, 2

• Systemic thrombolysis as primary treatment in intermediate- or low-risk PE
• Inferior vena cava filter insertion
• D-dimer testing in patients with high clinical probability of PE
• CT venography as adjunct to CTPA
• MRA to rule out PE

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Post-PE Follow-Up and CTEPH Screening

Routinely re-evaluate all patients 3-6 months after acute PE to screen for chronic thromboembolic pulmonary hypertension (CTEPH). 1, 2

• Refer symptomatic patients with mismatched perfusion defects on V/Q scan beyond 3 months to a pulmonary hypertension/CTEPH expert center 1
• Consider echocardiography, natriuretic peptide levels, and cardiopulmonary exercise testing in the evaluation 1
• Implement integrated care models to ensure optimal transition from hospital to ambulatory care 1

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Monitoring During Extended Anticoagulation

In patients receiving extended anticoagulation, reassess at regular intervals: 1, 2

• Drug tolerance and adherence
• Hepatic and renal function
• Bleeding risk assessment
• Consider occult malignancy workup in unprovoked VTE 2

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Key Clinical Pitfalls to Avoid

• Do not delay anticoagulation in high or intermediate clinical probability PE while awaiting imaging confirmation 4, 3, 5
• Do not assume NOAC failure without first confirming adherence and correct dosing 2
• Do not use aggressive fluid boluses in RV failure, as they worsen RV afterload—use vasopressors (norepinephrine/dobutamine) instead 3
• Do not use INR to monitor rivaroxaban or apixaban activity, as INR does not correlate reliably with drug levels 2
• Do not continue apixaban in triple-positive antiphospholipid syndrome—switch to warfarin 2