Treatment of Pulmonary Embolism
Direct oral anticoagulants (DOACs), specifically rivaroxaban or apixaban, are now the first-line treatment for most patients with confirmed pulmonary embolism, replacing the traditional warfarin-based regimens. 1, 2, 3
Risk Stratification Determines Treatment Approach
Treatment intensity must be guided by hemodynamic status and right ventricular function:
High-risk PE (hemodynamic instability with systolic hypotension or cardiogenic shock) requires immediate unfractionated heparin (UFH) intravenously—80 U/kg bolus followed by 18 U/kg/h continuous infusion—without waiting for diagnostic confirmation, plus mandatory systemic thrombolysis unless absolute contraindications exist 1, 2, 3
Intermediate-risk PE (hemodynamically stable but with RV dysfunction on imaging or elevated cardiac biomarkers) should be treated with DOAC or LMWH anticoagulation 1
Low-risk PE (hemodynamically stable without RV dysfunction or myocardial injury) should be treated with DOAC or LMWH anticoagulation 1
Anticoagulation Regimen for Stable Patients
First-Line: Direct Oral Anticoagulants
Rivaroxaban and apixaban are preferred over vitamin K antagonists for all eligible patients because they eliminate the need for parenteral bridging and INR monitoring 1, 2, 3:
Rivaroxaban dosing: 15 mg orally twice daily for 3 weeks, then 20 mg once daily 2, 4
Apixaban dosing: Higher dose during the first week, then maintenance dosing 2, 5
Both agents are FDA-approved for PE treatment and can be initiated immediately without parenteral anticoagulation overlap 4, 5, 4
Alternative: Traditional Approach with Parenteral Bridge
When DOACs are not suitable, use LMWH or fondaparinux subcutaneously followed by warfarin, overlapping until INR reaches 2.0-3.0 (target 2.5) for 2 consecutive days 6, 2, 3
High-Risk PE: Aggressive Intervention Protocol
For hemodynamically unstable patients, follow this sequence:
Immediate UFH without diagnostic delay: 80 U/kg IV bolus, then 18 U/kg/h infusion, adjusted to maintain aPTT 1.5-2.5 times control (46-70 seconds) 1, 2
Systemic thrombolytic therapy is mandatory unless absolute contraindications exist 1, 3
Surgical pulmonary embolectomy if thrombolysis is contraindicated or has failed 3
Special Populations Requiring Modified Approaches
Cancer Patients
LMWH is the preferred initial and long-term treatment for cancer-associated PE due to superior efficacy over warfarin in this population 6, 1, 3:
Dalteparin dosing: 200 IU/kg once daily for 1 month, then 150 IU/kg once daily for at least 5 months 6, 2
Apixaban is an effective alternative in cancer patients 1, 2
Pregnant Patients
Therapeutic fixed doses of LMWH based on early pregnancy weight are recommended, with mandatory consultant review and maternity services discussion prior to discharge 1, 3
Severe Renal Impairment
UFH is preferred when creatinine clearance is <30 mL/min for rivaroxaban, dabigatran, and edoxaban, or <25 mL/min for apixaban 6, 2, 3
Antiphospholipid Antibody Syndrome
DOACs are contraindicated; indefinite anticoagulation with a vitamin K antagonist is mandatory 3
Duration of Anticoagulation
All patients require at least 3 months of therapeutic anticoagulation 6, 3:
Provoked PE (associated with transient/reversible risk factors like surgery, trauma, immobilization): Discontinue after 3 months once the risk factor no longer exists 6, 1, 3
Unprovoked PE (no identifiable risk factor): Continue indefinitely, as recurrence rates are approximately 4.5% per year after discontinuation versus 2.5% for provoked PE 6, 1, 3
Cancer-associated PE: Indefinite anticoagulation is recommended due to ~20% recurrence rate in the first 12 months 6, 1
Recurrent VTE: Indefinite anticoagulation 3
Critical Pitfalls to Avoid
Never delay anticoagulation while awaiting diagnostic confirmation in patients with high or intermediate clinical probability 1, 2
Never stop parenteral anticoagulation before achieving therapeutic INR for 2 consecutive days when transitioning to warfarin 1, 2
Avoid aggressive fluid resuscitation in high-risk PE, as it worsens right ventricular failure 1, 2
Avoid routine use of inferior vena cava filters—only consider for absolute contraindications to anticoagulation or recurrent PE despite therapeutic anticoagulation 1
Never prematurely discontinue anticoagulation without considering coverage with another anticoagulant, as this increases thrombotic event risk 4