How should pulmonary embolism be managed, including anticoagulation, indications for thrombolysis, and duration of therapy?

Management of Pulmonary Embolism

Initial Risk Stratification and Anticoagulation

For hemodynamically unstable PE (systolic BP <90 mmHg or cardiogenic shock), immediately start unfractionated heparin (80 U/kg IV bolus followed by 18 U/kg/h continuous infusion) and proceed directly to systemic thrombolysis without waiting for diagnostic confirmation. 1

High-Risk (Massive) PE

• Administer systemic thrombolytic therapy immediately with alteplase 100 mg infused over 2 hours concurrently with unfractionated heparin 2, 1
• Target aPTT 1.5–2.5 times control (approximately 45–75 seconds), checking 4–6 hours after bolus and 6–10 hours after any dose adjustment 1, 3
• If thrombolysis is absolutely contraindicated or fails, proceed to surgical pulmonary embolectomy 2, 1
• Catheter-directed embolectomy or fragmentation may be considered as an alternative to surgery when thrombolysis is contraindicated or ineffective 2, 1

Non-High-Risk (Stable) PE

For hemodynamically stable patients, prefer direct oral anticoagulants (DOACs) as single-drug regimens over vitamin K antagonists. 1, 4

• Rivaroxaban: 15 mg orally twice daily for 21 days, then 20 mg once daily—no parenteral lead-in required 1, 4
• Apixaban: 10 mg orally twice daily for 7 days, then 5 mg twice daily—no parenteral lead-in required 1, 4
• Dabigatran or edoxaban: Require therapeutic LMWH for at least 5 days before switching to oral agent 1, 4

Alternative parenteral options when DOACs are not suitable:

• LMWH or fondaparinux are preferred over UFH in stable patients due to lower bleeding risk and no need for monitoring 2, 1
• UFH is reserved for severe renal impairment (CrCl <30 mL/min) or high bleeding risk because it is not renally cleared and can be rapidly reversed 2, 1

Thrombolysis Indications

Systemic thrombolysis is indicated ONLY for high-risk PE with cardiogenic shock or persistent hypotension—this is a Class I, Level A recommendation. 2, 1

Routine thrombolysis in intermediate-risk or low-risk PE is NOT recommended and represents a Class III (harm) recommendation. 1, 5

• Rescue thrombolytic therapy may be considered in intermediate-risk PE only if the patient develops hemodynamic deterioration (hypotension, shock, vasopressor requirement) despite adequate anticoagulation 2, 1, 5
• Do not use thrombolysis in low-risk PE under any circumstances 2

Duration of Anticoagulation Therapy

All patients with acute PE require a minimum of 3 months of therapeutic anticoagulation. 2, 1, 4

Decision Algorithm for Duration:

Provoked PE (major transient risk factor such as surgery, trauma, immobilization):

• Stop anticoagulation after 3 months 2, 1, 4

Unprovoked PE or recurrent VTE:

• Continue anticoagulation indefinitely 2, 1, 4
• After 6 months of full-dose therapy, consider dose reduction to apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily to reduce bleeding risk while maintaining efficacy 1, 4

Cancer-associated PE:

• Use therapeutic LMWH (not DOACs) as initial and long-term treatment for minimum 6 months and continue as long as cancer is active 2, 1, 5
• Cancer patients have three-fold higher recurrence risk and six-fold higher bleeding risk compared to non-cancer patients 4

Transition to Vitamin K Antagonists (When DOACs Contraindicated)

When using warfarin, overlap with parenteral anticoagulation (LMWH or UFH) for at least 5 days AND until INR is 2.0–3.0 for two consecutive days before stopping parenteral therapy. 2, 1, 4

• Target INR 2.5 (range 2.0–3.0) throughout treatment 2, 4
• Starting dose: 10 mg daily in younger adults (<60 years), ≤5 mg daily in older adults 4
• Monotherapy with warfarin without initial heparin leads to three-fold higher risk of recurrent VTE 1

Absolute Contraindications to DOACs

Switch to warfarin or LMWH in the following situations:

• Severe renal impairment (CrCl <30 mL/min for rivaroxaban/apixaban; <15 mL/min absolute) 1, 4
• Triple-positive antiphospholipid antibody syndrome (use warfarin with target INR 2.0–3.0) 1, 4
• Pregnancy or lactation (use therapeutic LMWH throughout pregnancy and ≥6 weeks postpartum) 1, 4
• Active cancer (prefer LMWH monotherapy) 1, 5

Common Pitfalls to Avoid

• Do NOT order D-dimer in patients with high clinical probability of PE—a negative result cannot safely exclude PE 1, 4
• Do NOT use INR to monitor rivaroxaban or apixaban—INR does not correlate with DOAC levels 4
• Do NOT routinely place inferior vena cava filters—they are not recommended for standard PE management 1, 4
• Do NOT delay anticoagulation while awaiting diagnostic confirmation in patients with high or intermediate clinical probability 2, 1
• Do NOT use aggressive fluid challenge in PE patients—vasopressors are preferred for hypotension 2

Follow-Up and Monitoring

• Routine clinical follow-up at 3–6 months after acute PE to screen for chronic thromboembolic pulmonary hypertension (CTEPH) 1, 4
• Refer symptomatic patients with mismatched perfusion defects on V/Q scan beyond 3 months to a pulmonary hypertension expert center 1, 4
• During extended anticoagulation, regularly reassess drug tolerance, adherence, hepatic and renal function, and bleeding risk 1, 4