Treatment of Pulmonary Thromboembolism
Immediate anticoagulation is the cornerstone of PE treatment, with the specific regimen determined by hemodynamic status: high-risk PE requires unfractionated heparin plus systemic thrombolysis, while intermediate- and low-risk PE should be treated with LMWH or fondaparinux followed by a direct oral anticoagulant (DOAC) rather than warfarin. 1
Risk Stratification Determines Treatment Intensity
The first critical step is determining PE severity, as this dictates whether you anticoagulate alone or add reperfusion therapy 1, 2, 3:
- High-risk PE = shock or persistent hypotension (systolic BP <90 mmHg for ≥15 minutes or requiring vasopressor support) 1
- Intermediate-risk PE = hemodynamically stable but with right ventricular dysfunction on imaging or elevated cardiac biomarkers 1
- Low-risk PE = hemodynamically stable without RV dysfunction 1
High-Risk (Massive) PE: Aggressive Reperfusion
For patients in shock or with persistent hypotension, systemic thrombolysis is first-line treatment and should be administered immediately 1. The 2019 ESC guidelines give this a Class I, Level B recommendation—the strongest evidence-based endorsement 1.
Immediate Actions for High-Risk PE:
- Start unfractionated heparin (UFH) immediately with weight-adjusted bolus (80 IU/kg or 5,000-10,000 units) followed by continuous infusion (18 IU/kg/hour or 1,250-1,300 IU/hour), targeting aPTT 1.5-2.5 times control 1, 2, 3
- Administer systemic thrombolysis unless absolute contraindications exist 1
- Vasopressor support with norepinephrine and/or dobutamine for hypotension 1, 2, 3
When Thrombolysis Fails or Is Contraindicated:
- Surgical pulmonary embolectomy is recommended (Class I, Level C) 1, 3
- Percutaneous catheter-directed treatment should be considered (Class IIa, Level C) 1, 3
- ECMO may be considered in combination with surgical or catheter-directed treatment for refractory circulatory collapse 1
Critical pitfall: UFH is specifically required for high-risk PE rather than LMWH because it can be rapidly reversed if bleeding occurs or emergency surgery becomes necessary 1, 2. Stop heparin before administering thrombolysis, then resume at maintenance dose afterward 1.
Intermediate- and Low-Risk PE: Anticoagulation Protocol
For hemodynamically stable patients, LMWH or fondaparinux is preferred over UFH (Class I, Level A recommendation) 1, 2, 3. This represents a significant evolution from older guidelines that favored UFH universally 1.
Initial Parenteral Anticoagulation:
- LMWH or fondaparinux should be started immediately, even before imaging confirmation if clinical probability is intermediate or high 1
- LMWH has equal efficacy and safety to UFH but is easier to use 1, 4
- Do not wait for diagnostic confirmation to start anticoagulation in patients with intermediate or high clinical probability 1
Transition to Oral Anticoagulation:
When initiating oral anticoagulation, a DOAC (apixaban, rivaroxaban, edoxaban, or dabigatran) is recommended over warfarin (Class I, Level A) 1, 3. This is the most recent and highest-quality evidence available, superseding older warfarin-based protocols 1.
DOAC Regimens (FDA-approved for PE treatment):
- Apixaban: 10 mg twice daily for 7 days, then 5 mg twice daily 5
- Rivaroxaban: 15 mg twice daily for 21 days, then 20 mg once daily 6
- Both can be started immediately without requiring parenteral overlap 5, 6, 7
When DOACs Are Contraindicated:
NOACs should NOT be used in 1, 2:
- Severe renal impairment (CrCl <30 mL/min)
- Pregnancy and lactation
- Antiphospholipid antibody syndrome
For these patients, use warfarin with parenteral anticoagulation overlap until INR reaches 2.0-3.0 for at least 24 hours, then discontinue heparin 1.
Warfarin Protocol (when DOACs contraindicated):
- Start 5-10 mg daily for 2 days 1
- Target INR 2.0-3.0 1
- Continue parenteral anticoagulation for minimum 5 days AND until INR ≥2.0 for 24 hours 1
- Monitor INR every 1-2 days initially, then adjust frequency 1
Duration of Anticoagulation
The treatment duration depends on whether PE was provoked or unprovoked 1, 3:
- Provoked PE (temporary risk factors like surgery, trauma, immobilization): 3 months minimum, can discontinue after 3-6 months 1, 3
- First unprovoked PE: Minimum 3 months, consider indefinite anticoagulation after reassessing bleeding risk 1, 3
- Recurrent VTE or ongoing risk factors: At least 6 months, often indefinite 1
- Cancer-associated PE: LMWH for at least 6 months, continue as long as cancer is active 3
Special Situations
Inferior Vena Cava Filters:
IVC filters should be considered only in two specific scenarios (Class IIa, Level C) 1, 2, 3:
- Absolute contraindications to anticoagulation
- Recurrent PE despite therapeutic anticoagulation
Routine use of IVC filters is NOT recommended (Class III, Level A) 1. This is strong evidence against their widespread use 1.
Rescue Thrombolysis:
If a patient deteriorates hemodynamically while on anticoagulation, rescue thrombolysis is recommended (Class I, Level B) 1. Alternatively, surgical embolectomy or catheter-directed treatment should be considered 1.
Critical pitfall: Routine primary thrombolysis is NOT recommended for intermediate- or low-risk PE (Class III, Level B) 1. Only use thrombolysis for high-risk PE or rescue situations.
Early Discharge and Outpatient Management:
Carefully selected low-risk PE patients should be considered for early discharge and home treatment (Class IIa, Level A) 1. This requires proper outpatient anticoagulation monitoring and follow-up 1.
Monitoring Requirements
For UFH:
- Check aPTT 4-6 hours after initial bolus 1
- Check aPTT 6-10 hours after any dose change 1
- Daily aPTT once therapeutic range achieved (1.5-2.5 times control or 45-75 seconds) 1
For Warfarin:
For DOACs:
Follow-Up
All patients should be reassessed at 3-6 months post-PE to evaluate for persistent dyspnea, functional limitation, or chronic thromboembolic pulmonary hypertension 3. At 6-12 weeks, determine whether to continue or discontinue anticoagulation based on risk factors 1.