Platelet transfusion refractoriness (PTR) represents a major challenge in the transfusion support of patients with severe thrombocytopenia, particularly those with hematologic malignancies, intensive chemotherapy, or hematopoietic stem cell transplantation. Although nonimmune mechanisms account for the majority of cases, immune-mediated PTR caused by alloantibodies against platelet antigens, most commonly human leukocyte antigen (HLA) class I molecules, remains clinically important. This review summarizes current knowledge on the definition, mechanisms, diagnostic evaluation, and management of immune PTR. The immunologic basis of platelet destruction in immune PTR involves several mechanisms mediated by anti-HLA antibodies, including Fc receptor-dependent phagocytosis, complement activation, and antibody-induced platelet activation. Diagnostic evaluation integrates clinical assessment with laboratory detection of HLA antibodies, molecular HLA typing, and platelet crossmatching. Clinical management primarily relies on the provision of compatible platelet products, including HLA-matched platelets, antibody-specific antigen-negative platelet units, or crossmatched platelet concentrates. In selected cases, additional testing for antibodies against human platelet antigens (HPAs) may be required. Preventive strategies such as leukoreduction have substantially reduced the incidence of alloimmunization, although immune PTR continues to occur in a subset of transfusion-dependent patients. Emerging strategies aimed at improving transfusion outcomes include approaches to reduce platelet immunogenicity, development of HLA-deficient platelets, and pharmacologic interventions targeting antibody-mediated platelet clearance. A better understanding of the mechanisms underlying immune PTR may help refine diagnostic algorithms and expand therapeutic options for patients requiring long-term platelet transfusion support.

Received: 07 April 2026

Accepted after revision: 01 June 2026

Article published online:
22 June 2026

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