Immune-mediated platelet refractoriness: Mechanisms, diagnostics, and therapeutic breakthroughs

Platelets are increasingly recognised as key mediators of immunity, contributing to clinical challenges such as platelet transfusion refractoriness (PTR). While predominantly driven by non-immune factors, immune-mediated PTR-primarily due to alloimmunisation against human leukocyte antigens (HLA) and/or human platelet antigens (HPA)-presents distinct management difficulties. Current therapies are often suboptimal, and emerging strategies require validation. This review synthesises current knowledge on antibody pathogenesis, advanced detection methods, and novel therapies for immune-mediated PTR, aiming to inform clinical decision-making and future research. A comprehensive literature review was conducted, focusing on peer-reviewed articles addressing immune-mediated PTR, mechanisms of alloimmunisation, diagnostic techniques for HLA/HPA antibodies, and therapeutic innovations. Key studies and emerging data were analysed to evaluate current evidence and identify knowledge gaps. Immune-mediated PTR arises primarily from alloantibodies against HLA class I and/or HPA, leading to accelerated platelet clearance. Advanced detection methods, including multiplex bead arrays and genotyping platforms, have improved identification of incompatible donors. Current management relies on provision of antigen-negative or crossmatch-compatible platelets, with immunosuppressive therapy reserved for refractory cases. Novel strategies such as platelet genome editing, antibody inhibition, and nanoparticle-based immune modulation are under investigation, but robust clinical validation is lacking. This review highlights the central role of alloimmunisation in immune-mediated PTR and the importance of accurate antibody detection and antigen matching. While existing therapies remain suboptimal for some patients, emerging technologies hold potential but require further clinical evaluation. Improved understanding of pathogenesis and validation of novel approaches are essential to advance management and reduce the burden of PTR.