What safety netting advice is recommended for patients with large volume bilateral unprovoked pulmonary embolisms (PEs) while on Apixaban (apixaban)?

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From the Guidelines

Safety Netting Advice for Patients with Large Volume Bilateral Unprovoked Pulmonary Embolisms (PEs) on Apixaban

For patients experiencing large volume bilateral unprovoked pulmonary embolisms (PEs) while on apixaban, immediate discontinuation of apixaban and initiation of therapeutic anticoagulation is crucial. This can be achieved with unfractionated heparin (UFH) at a dose of 80 units/kg bolus followed by 18 units/kg/hour infusion, or low molecular weight heparin (LMWH) such as enoxaparin at a dose of 1 mg/kg twice daily 1.

Transition to More Potent Anticoagulant

Patients should be transitioned to a more potent anticoagulant, such as:

  • Rivaroxaban at a dose of 15 mg twice daily for 21 days, followed by 20 mg once daily 1, or
  • Warfarin with a target international normalized ratio (INR) of 2.5 1.

Close Monitoring

Close monitoring for signs and symptoms of recurrent venous thromboembolism (VTE) and anticoagulant-related bleeding is essential, with regular follow-up appointments and laboratory assessments 1.

Extended Anticoagulation

Extended anticoagulation of indefinite duration should be considered for patients with a first episode of PE and no identifiable risk factor, or those with a first episode of PE associated with a persistent risk factor other than antiphospholipid antibody syndrome 1. If extended oral anticoagulation is decided after PE in a patient without cancer, a reduced dose of the NOACs apixaban (2.5 mg b.i.d.) or rivaroxaban (10 mg o.d.) should be considered after 6 months of therapeutic anticoagulation 1.

Key Considerations

  • The patient’s bleeding risk should be assessed to identify and treat modifiable bleeding risk factors, which may influence decision-making on the duration and regimen/dose of anticoagulant treatment 1.
  • Periodic reassessment of the risk-to-benefit ratio of continued anticoagulant treatment is mandatory 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Safety Netting Advice for Patients with Large Volume Bilateral Unprovoked Pulmonary Embolisms (PEs) on Apixaban

  • The optimal treatment regimen for patients with unprovoked pulmonary embolism (PE) remains unclear, but apixaban may be a preferable treatment option due to its lower risk of severe bleeding and reduced PE recurrence 2.
  • Extended anticoagulation is offered to patients with unprovoked PE or proximal deep vein thrombosis (DVT) and a low risk of bleeding 3.
  • In patients with unprovoked PE or proximal DVT and a low risk of bleeding, who want to stop anticoagulation after 3 months, further risk stratification is necessary using clinical scoring systems and thrombophilia testing 3.
  • New oral anticoagulants such as apixaban may be preferred to vitamin K antagonists in patients without cancer or renal failure, especially after the development of reversal agents 3.
  • Apixaban has been shown to have a lower risk of recurrent VTE, major bleeding, and clinically relevant non-major bleeding compared to low-molecular-weight heparin (LMWH) in patients with cancer-associated VTE 4.
  • Apixaban has also been shown to have a lower risk of recurrent VTE and bleeding compared to rivaroxaban in patients with VTE 5.

Key Considerations

  • Patients with large volume bilateral unprovoked PEs on apixaban should be closely monitored for signs of recurrent VTE and bleeding.
  • Regular follow-up appointments and laboratory tests may be necessary to assess the patient's risk of recurrent VTE and bleeding.
  • Patients should be educated on the signs and symptoms of recurrent VTE and bleeding, and instructed to seek medical attention immediately if they experience any of these symptoms.
  • The decision to extend or stop anticoagulation should be made on a case-by-case basis, taking into account the patient's individual risk factors and medical history.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

An Algorithmic Approach to Management of Venous Thromboembolism.

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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