What is the recommended treatment for pulmonary embolism?

Treatment of Pulmonary Embolism

For most patients with confirmed pulmonary embolism, initiate anticoagulation immediately with a direct oral anticoagulant (DOAC)—specifically rivaroxaban or apixaban as single-drug regimens—which are now preferred over warfarin and low-molecular-weight heparin (LMWH) combinations for eligible patients. 1, 2, 3

Risk Stratification Determines Treatment Intensity

Before selecting your anticoagulation strategy, classify the patient based on hemodynamic stability:

• High-risk PE: Hemodynamic instability with systolic hypotension (<90 mmHg) or cardiogenic shock requiring vasopressors 2, 4
• Intermediate-risk PE: Hemodynamically stable but with right ventricular dysfunction on imaging or elevated cardiac biomarkers 2, 4
• Low-risk PE: Hemodynamically stable without RV dysfunction or myocardial injury 2, 4

High-Risk PE: Aggressive Intervention Required

For hemodynamically unstable patients, immediately administer unfractionated heparin (UFH) intravenously without waiting for diagnostic confirmation. 1, 2, 3

UFH Dosing Protocol:

• Initial bolus: 80 U/kg IV 1, 3
• Continuous infusion: 18 U/kg/h 1, 3
• Adjust based on aPTT to maintain 1.5-2.5 times control value (46-70 seconds) 1, 3

aPTT-Based Dose Adjustments:

• aPTT <35 seconds: Give 80 U/kg bolus; increase infusion by 4 U/kg/h 1
• aPTT 35-45 seconds: Give 40 U/kg bolus; increase infusion by 2 U/kg/h 1
• aPTT 46-70 seconds: No change 1
• aPTT 71-90 seconds: Reduce infusion by 2 U/kg/h 1
• aPTT >90 seconds: Stop infusion for 1 hour, then reduce by 3 U/kg/h 1

Reperfusion Therapy:

Systemic thrombolytic therapy is mandatory for all high-risk PE patients unless absolute contraindications exist. 1, 2, 4

• If thrombolysis is contraindicated or fails, proceed to surgical pulmonary embolectomy 1, 2, 4
• Catheter-directed therapy is an alternative when thrombolysis is contraindicated or has failed 2, 4

Hemodynamic Support:

• Consider norepinephrine and/or dobutamine for hemodynamic support 2
• Avoid aggressive fluid resuscitation as it worsens right ventricular failure 3

Intermediate and Low-Risk PE: Anticoagulation Strategy

First-Line: Direct Oral Anticoagulants (DOACs)

DOACs are preferred over vitamin K antagonists for all eligible patients. 1, 2, 3, 4

Rivaroxaban (Single-Drug Regimen):

• 15 mg orally twice daily for 3 weeks 3, 5
• Then 20 mg once daily for maintenance 3, 5
• No parenteral anticoagulation required 1, 3

Apixaban (Single-Drug Regimen):

• 10 mg orally twice daily for 7 days 6
• Then 5 mg twice daily for maintenance 6
• No parenteral anticoagulation required 1, 3
• Effective alternative in cancer patients 3

Dabigatran or Edoxaban (Requires Parenteral Lead-In):

• Requires at least 5-10 days of parenteral anticoagulation (LMWH or fondaparinux) before initiation 1, 3
• Less practical than rivaroxaban or apixaban 1

Alternative: LMWH or Fondaparinux Followed by Warfarin

If DOACs are not suitable:

LMWH Options:

• Enoxaparin: 1.0 mg/kg subcutaneously every 12 hours OR 1.5 mg/kg once daily 1
• Tinzaparin: 175 U/kg subcutaneously once daily 1

Fondaparinux (Weight-Adjusted):

• <50 kg: 5 mg subcutaneously once daily 1
• 50-100 kg: 7.5 mg subcutaneously once daily 1
• >100 kg: 10 mg subcutaneously once daily 1

Transition to Warfarin:

• Overlap parenteral anticoagulation with warfarin until INR reaches 2.5 (range 2.0-3.0) for 2 consecutive days 1, 3, 4
• Never stop parenteral anticoagulation prematurely 3

Absolute Contraindications to DOACs

Do not use DOACs in the following situations: 1, 2, 4

• Severe renal insufficiency: Creatinine clearance <30 mL/min for rivaroxaban, dabigatran, edoxaban; <25 mL/min for apixaban 1
• Pregnancy and lactation 1, 2, 4
• Antiphospholipid antibody syndrome 1, 2, 4

In these cases, use UFH (for severe renal dysfunction) or LMWH (for pregnancy and cancer) 3, 7

Special Populations

Cancer Patients:

LMWH is the preferred initial and long-term treatment. 1, 3, 4

• Dalteparin: 200 IU/kg subcutaneously once daily for 1 month, then 150 IU/kg once daily for 5 months 3
• Apixaban is an effective alternative 3

Pregnant Patients:

• Therapeutic fixed doses of LMWH based on early pregnancy weight 4
• All pregnant women with suspected or confirmed PE should be reviewed by a consultant and discussed with maternity services prior to discharge 1

Severe Renal Dysfunction (CrCl <30 mL/min):

• UFH is preferred 3
• Avoid DOACs 1

Duration of Anticoagulation

Provoked PE (Transient/Reversible Risk Factor):

Discontinue anticoagulation after 3 months. 1, 2, 4

Unprovoked PE or Recurrent VTE:

Continue anticoagulation indefinitely. 2, 4

Antiphospholipid Antibody Syndrome:

Indefinite anticoagulation with a vitamin K antagonist (VKA) is mandatory. 2, 4

Critical Pitfalls to Avoid

• Never delay anticoagulation while awaiting diagnostic confirmation in patients with high or intermediate clinical probability 3
• Do not use LMWH or fondaparinux in hemodynamically unstable patients—use UFH only 1
• Do not stop parenteral anticoagulation before achieving therapeutic INR for 2 consecutive days when using warfarin 3
• Avoid routine use of inferior vena cava filters—only consider for absolute contraindications to anticoagulation or recurrent PE despite therapeutic anticoagulation 2, 4
• Do not use aggressive fluid resuscitation in high-risk PE 3

Outpatient Management for Low-Risk Patients

Carefully selected low-risk patients (PESI class I/II or sPESI score 0) should be considered for early discharge and home treatment. 1, 2, 4

Exclusion Criteria for Outpatient Management:

• Active bleeding or high bleeding risk 1
• Already on full-dose anticoagulation at time of PE 1
• Severe pain requiring opiates 1
• CKD stages 4 or 5 (eGFR <30 mL/min) or severe liver disease 1
• Heparin-induced thrombocytopenia within the last year 1
• Social reasons (inability to return home, inadequate care, lack of telephone communication, compliance concerns) 1

Use a single DOAC in outpatient pathways (rivaroxaban or apixaban) to minimize confusion over dosing 1