Pulmonary Embolism in Antiphospholipid Syndrome (APS)—Where Are We and Where Are We Going?

TL;DR

This review discusses the challenges and future directions in managing pulmonary embolism in antiphospholipid syndrome, a condition linked to blood clots and autoimmune factors.

Contribution

The paper provides a comprehensive overview of current knowledge and future therapeutic strategies for pulmonary embolism in APS.

Findings

Triple-positive aPLA profiles significantly increase the risk of recurrent pulmonary embolism and long-term complications like CTEPH.

Long-term vitamin K antagonists are the standard treatment, while direct oral anticoagulants are not recommended for high-risk APS patients.

Future strategies include better risk assessment using aPLA profiling and targeted therapies like complement inhibition.

Abstract

Pulmonary embolism (PE) is one of the most serious complications of antiphospholipid syndrome (APS), a systemic autoimmune disorder defined by thrombotic events and persistent antiphospholipid antibodies (aPLA). PE occurs in 11–20% of patients and may constitute the initial clinical manifestation. Young and middle-aged women are most frequently affected, and triple-positive aPLA profiles markedly increase the risk of recurrence and long-term morbidity, including chronic thromboembolic pulmonary hypertension (CTEPH). This review article summarizes current evidence on the epidemiology, pathophysiology, diagnostic approach, and management of PE in APS. Key mechanisms include anti-β2-glycoprotein I-mediated endothelial and platelet activation, complement engagement, and neutrophil extracellular trap formation, resulting in immunothrombosis. Diagnostic pathways follow standard PE algorithms; however, chronically elevated D-dimer levels and lupus anticoagulant-related aPTT prolongation require careful interpretation and consideration. Long-term vitamin K antagonist therapy remains the standard of care, whereas direct oral anticoagulants are not recommended in high-risk APS. Future directions include improved risk stratification through detailed aPLA profiling and the use of emerging biomarkers, early screening for CTEPH, and the development of targeted therapies such as complement inhibition and anti-NETosis strategies.

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