Platelet-leukocyte aggregates in cardiovascular disease: prognostic significance and therapeutic potential

Initially recognized for their role in vascular haemostasis, platelets are now understood to be critical regulators of inflammation and immune responses through complex interactions with immune cells. Key to this role is the formation of platelet-leukocyte aggregates (PLAs), with platelet-monocyte aggregates (PMAs) representing the most thoroughly studied type in cardiovascular disease. PLAs form through the binding of platelet surface P-selectin to P-selectin glycoprotein ligand on leukocytes, an early interaction that may trigger broader inflammatory cascades. Recent studies link circulating PMAs with in vivo platelet activation and elevated PMA levels in patients with high thrombogenic risk, such as those with diabetes and acute myocardial infarction. Furthermore, PMA levels correlate with disease severity and long-term cardiovascular outcomes, highlighting their potential as prognostic biomarkers for adverse cardiovascular events. Therapeutic strategies, such as antiplatelet agents and P-selectin antagonists, have demonstrated efficacy in the inhibition of PLA formation. However, the development of selective inhibitors that preserve the haemostatic and immune functions of platelets remains an unmet clinical need. Despite significant progress, the precise biological functions and underlying mechanisms of PLAs are not fully understood. This review integrates preclinical and clinical data to provide a comprehensive overview of platelet-leukocyte biology, with a focus on the prognostic role and therapeutic potential of PLAs in cardiovascular disease.