Thrombocytosis and the generation of platelet‐derived microparticles in the pathophysiology of sickle cell disease

Sickle cell disease (SCD) is a complex thrombo-inflammatory disorder in which haemolysis, platelet activation, thrombocytosis, inflammation and endothelial activation operate as an intricate network creating a perpetual cycle of cellular injury and vascular dysfunction that drives vaso-occlusive crises, tissue ischaemia and progressive end-organ damage. Thrombocytosis is common in SCD, especially in response to acute chest syndrome, vaso-occlusive crises and chronic haemolysis. Increased platelet activity contributes to the proinflammatory and prothrombotic environment. Activated platelets release platelet-derived microparticles (PMPs) containing phospholipids and inflammatory mediators, which enhance thrombin generation, entrap leucocytes and promote cellular adhesions leading to endothelial dysfunction and vaso-occlusion within the microvasculature. This review provides insights into the mechanisms underlying thrombocytosis and PMP formation in SCD and discusses therapeutic strategies targeting platelet activation to mitigate inflammation and vascular complications.