Treatment of Pulmonary Embolism
Immediate anticoagulation is the cornerstone of PE treatment, with the specific approach determined by hemodynamic stability: high-risk PE requires IV unfractionated heparin plus systemic thrombolysis, while hemodynamically stable PE is best treated with direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, edoxaban, or dabigatran. 1, 2
Risk Stratification Determines All Management
Risk stratification must be performed immediately upon PE diagnosis, as this dictates every subsequent treatment decision 1, 3:
- High-risk (massive) PE: Systolic blood pressure <90 mmHg, cardiac arrest, hemodynamic collapse requiring vasopressors, or cardiogenic shock 1, 3
- Intermediate-risk (submassive) PE: Hemodynamically stable but with right ventricular dysfunction on imaging or elevated cardiac biomarkers 1, 3
- Low-risk PE: Hemodynamically stable without RV dysfunction 1, 3
High-Risk PE: Aggressive Intervention Required
Immediate Anticoagulation
Initiate IV unfractionated heparin immediately with an 80 units/kg bolus followed by continuous infusion of 400-600 units/kg daily, titrated to maintain APTT 1.5-2.5 times control values. 4, 1, 3 LMWH and fondaparinux have not been tested in hypotensive/shock settings and should be avoided 4.
Thrombolytic Therapy
Systemic thrombolysis should be administered unless absolute contraindications exist, as it reduces mortality from 3.9% to 2.3% (1.6% absolute reduction). 2, 5 The American College of Cardiology recommends 1:
- 50 mg alteplase IV bolus if cardiac arrest is imminent
- 100 mg alteplase over 90 minutes if patient is more stable
Absolute contraindications to thrombolysis include hemorrhagic stroke at any time, ischemic stroke in preceding 6 months, CNS damage/neoplasms, recent major trauma/surgery/head injury, GI bleeding within last month, and known active bleeding 3.
Rescue Interventions
If thrombolysis is contraindicated or fails 4, 1, 3:
- Surgical pulmonary embolectomy is the preferred rescue therapy
- Catheter embolectomy or thrombus fragmentation may be considered if surgery unavailable, though safety/efficacy data are limited
Hemodynamic Support
- Administer vasopressors for hypotension 4
- Dobutamine or dopamine may be used for low cardiac output with normal blood pressure 4
- Avoid aggressive fluid challenge as it can worsen RV failure 4
- Provide supplemental oxygen if SaO₂ <90% 1
Intermediate-Risk and Low-Risk PE: Anticoagulation Strategy
First-Line Anticoagulation
Direct oral anticoagulants (DOACs) are superior to warfarin, with 0.6% lower bleeding rates and noninferior efficacy. 2, 6 For hemodynamically stable patients, LMWH or fondaparinux is preferred over unfractionated heparin for initial parenteral anticoagulation 7, 3:
LMWH dosing 7:
- Enoxaparin 1 mg/kg subcutaneously every 12 hours, OR
- Enoxaparin 1.5 mg/kg subcutaneously once daily
Fondaparinux dosing 7:
- 5 mg if <50 kg
- 7.5 mg if 50-100 kg
- 10 mg if >100 kg (all once daily subcutaneously)
- Apixaban, rivaroxaban, edoxaban, or dabigatran
- Do not use DOACs in severe renal impairment, pregnancy, or antiphospholipid syndrome 7
Traditional Warfarin Approach
If warfarin is used, overlap with parenteral anticoagulation for minimum 5-7 days until INR reaches 2.0-3.0 for two consecutive days, then continue warfarin targeting INR 2.5 (range 2.0-3.0) 7, 8.
Selective Thrombolysis for Intermediate-Risk PE
Thrombolysis may be considered for intermediate-risk PE on a case-by-case basis, particularly in patients without elevated bleeding risk and with evidence of clinical deterioration. 4, 5 However, this remains controversial as overall mortality is not significantly affected, though it reduces need for emergency rescue thrombolysis 4.
Duration of Anticoagulation
All patients require minimum 3 months of therapeutic anticoagulation. 1, 3, 8 Duration beyond 3 months depends on PE classification 1, 7, 8:
Provoked PE (transient/reversible risk factor)
Unprovoked PE (first episode)
- Continue 6-12 months minimum 7, 8
- Consider indefinite anticoagulation if bleeding risk is low-to-moderate, as recurrence risk exceeds 5% annually and reaches 50% within 10 years after stopping 7
High-Risk Features Favoring Indefinite Therapy 7:
- Second episode of unprovoked PE (strongly recommended)
- Documented antiphospholipid antibodies or multiple thrombophilic conditions
- Active cancer (use LMWH monotherapy, not DOACs)
- Deficiency of antithrombin, Protein C, or Protein S
- Factor V Leiden or prothrombin 20210 gene mutation
High Bleeding Risk Features Favoring Stopping at 3-6 Months 7:
- Age ≥80 years
- Previous major bleeding episodes
- Recurrent falls
- Need for dual antiplatelet therapy
- Severe renal or hepatic impairment
The risk-benefit ratio should be reassessed at regular intervals during indefinite treatment. 7, 8
Outpatient vs. Inpatient Management
Low-risk patients may be candidates for outpatient management using validated risk scores (PESI class I/II, sPESI 0, or Hestia criteria). 1
Exclusion criteria mandating hospital admission 1:
- Heart rate >110 bpm or systolic BP <100 mmHg
- Oxygen saturation <90% on room air
- Active bleeding or high bleeding risk
- Severe pain requiring opiates
- Other medical comorbidities requiring admission
Follow-Up Care
Routine clinical re-evaluation at 3-6 months post-PE is essential to assess for persistent dyspnea or functional limitation that may indicate chronic thromboembolic pulmonary hypertension (CTEPH). 1, 3
Critical Pitfalls to Avoid
- Never delay anticoagulation in high-risk PE while awaiting confirmatory imaging if clinical suspicion is high 4
- Do not use LMWH or fondaparinux in hemodynamically unstable patients—only unfractionated heparin has been studied in this setting 4
- Avoid stopping anticoagulation prematurely in unprovoked PE, as recurrence risk persists indefinitely and benefit only continues while on therapy 7
- Do not use reduced-intensity anticoagulation routinely, as it is less effective than conventional intensity 7
- Monitor platelet count if heparin continued beyond 5 days due to risk of heparin-induced thrombocytopenia 4