Antiplatelet therapy in pulmonary embolism: Mechanisms and evidence

Abstract

Pulmonary embolism (PE) is a common and potentially fatal manifestation of venous thromboembolism, typically resulting from thrombus formation in the venous circulation and subsequent embolization to the pulmonary arterial tree. Its pathobiology reflects the convergence of venous stasis, hypercoagulability, and endothelial dysfunction, which together initiate a thrombo-inflammatory cascade involving coagulation factors, vascular cells, and innate immune pathways. Although PE thrombi have classically been characterized as fibrin- and erythrocyte-rich structures, accumulating evidence supports an active and regulatory role for platelets across key stages relevant to PE, including thrombus formation, embolization potential, clot stabilization, resolution, and recurrence. Anticoagulation remains the foundation of PE prevention and treatment, with low-molecular-weight heparins, vitamin K antagonists, and direct oral anticoagulants representing the main therapeutic options in contemporary practice. In contrast, the role of antiplatelet therapy in PE remains to be further investigated. While antiplatelet agents may provide modest benefit in selected clinical settings—such as specific prophylactic scenarios and secondary prevention after discontinuation of anticoagulation—their efficacy is generally inferior to anticoagulants, and they are not recommended as first-line therapy for acute PE management. Mechanistically, platelets can contribute to PE-related thrombogenesis by providing procoagulant surfaces, amplifying thrombin generation, and mediating crosstalk with endothelial and innate immune cells, particularly neutrophils and monocytes. These interactions promote immunothrombosis, neutrophil extracellular trap formation, and thrombus stabilization, reinforcing the link between inflammation and coagulation within the venous-to-pulmonary thromboembolic continuum. The primary objective of this review is to critically interpret the role of antiplatelet therapy specifically in PE by integrating recent preclinical insights with contemporary clinical evidence. By synthesizing advances in platelet biology, experimental models, and clinical studies, this article evaluates the therapeutic potential, limitations, and future directions of platelet-targeted strategies in PE. A deeper understanding of platelet-driven mechanisms may inform the development of safer, more precise antithrombotic approaches that complement established anticoagulant therapies and improve outcomes in patients with PE.