From the Guidelines
Recurrent unprovoked pulmonary embolism is most commonly caused by inherited or acquired thrombophilia disorders, and patients typically require extended or even lifelong anticoagulation therapy. The causes of recurrent unprovoked pulmonary embolism include:
- Inherited thrombophilia disorders, such as Factor V Leiden mutation, prothrombin gene mutation, protein C or S deficiency, and antithrombin deficiency
- Acquired thrombophilia disorders, such as antiphospholipid syndrome
- Occult malignancy, particularly pancreatic, lung, and hematologic cancers
- Chronic inflammatory conditions, such as inflammatory bowel disease or autoimmune disorders
- Anatomical abnormalities, such as May-Thurner syndrome or vascular malformations
According to the American Society of Hematology 2020 guidelines for management of venous thromboembolism 1, patients with unprovoked VTE have a high risk of recurrent VTE if anticoagulation is discontinued, with an estimated risk of 10% by 1 year and up to 30% by 5 to 10 years. The ASH guideline panel recommends continuing antithrombotic therapy indefinitely after completion of primary treatment for patients with unprovoked VTE, based on moderate certainty in the evidence of effects.
A comprehensive workup, including thrombophilia testing, age-appropriate cancer screening, and possibly CT imaging, should be performed to identify the underlying cause, as this may influence treatment decisions and duration 2. The choice of anticoagulant therapy, such as direct oral anticoagulants like apixaban (5mg twice daily) or rivaroxaban (20mg daily with food), or alternatively warfarin (target INR 2-3), should be individualized based on patient-specific factors, such as bleeding risk and comorbidities 3.
From the Research
Causes of Recurrent Unprovoked Pulmonary Embolism
- Recurrent pulmonary embolism can be caused by various factors, including underlying diseases such as heart disease, venous insufficiency, and malignancy 4
- The risk of recurrence is higher in patients with unprovoked pulmonary embolism, which occurs in the absence of any identifiable temporary or persistent risk factors for venous thromboembolism 5
- Obesity, immobilization, and other risk factors can also contribute to the development of recurrent pulmonary embolism 4
Risk Factors for Recurrence
- Patients with a history of deep vein thrombosis (DVT) or pulmonary embolism are at higher risk of recurrence 4
- The presence of underlying diseases such as heart disease, venous insufficiency, and malignancy can also increase the risk of recurrence 4
- The use of estrogen and other medications can also increase the risk of recurrence 6
Prevention and Treatment
- Anticoagulant treatment can reduce the risk of recurrent venous thromboembolism (VTE) by about 90% after index pulmonary embolism 7
- Direct oral anticoagulants (DOACs) such as apixaban, edoxaban, rivaroxaban, and dabigatran are effective in preventing recurrent VTE and have a lower risk of bleeding compared to traditional anticoagulants 8, 6
- The choice of anticoagulant therapy should be based on the balance between the estimated risk of recurrent VTE and the risk of bleeding 7