Platelet transfusion biology: from hemostatic support to inflammatory and immune signaling

Abstract

Platelet transfusion remains indispensable for the prevention and treatment of bleeding in hematology, oncology, transplantation, critical care, surgery and trauma. Yet the biological impact of a platelet concentrate extends well beyond numerical correction of thrombocytopenia. Platelets are anucleate but metabolically active immune cells that express pattern-recognition receptors, release cytokines, chemokines, lipid mediators, extracellular vesicles, mitochondria-derived material and damage-associated molecular patterns; and interact with leukocytes, endothelial cells and complement. During collection, processing and storage, platelet concentrates acquire a distinct productspecific phenotype shaped by donor biology, residual plasma, additive solutions, leukoreduction, pathogen reduction, temperature and storage time. These variables affect not only post-transfusion recovery and hemostatic function, but also inflammatory signaling and immune related complications. The recipient is equally important: sepsis, chemotherapy, malignancy, neonatal immune development, endothelial activation and prior alloimmunization can determine whether transfused platelets restore hemostasis, amplify inflammation, or trigger refractoriness. This review explores platelet transfusion through the lens of a biological triad formed by the donor, the platelet product, and the recipient. We focus on how platelet immune receptors, storage-induced inflammatory remodeling, soluble biological response modifiers, extracellular vesicles and complement shape the interactions of transfused platelets with recipient leukocytes and endothelium. Alloimmunization and refractoriness are considered more briefly as recipient-dependent modifiers of platelet recovery and transfusion efficacy. The central challenge is no longer to define a single optimal platelet product, but to engineer and select the right platelet product for the right patient, at the right moment.