Platelet desialylation, apoptosis, and T-lymphocyte-mediated immune dysregulation: unveiling the pathways of platelet clearance in platelet transfusion refractoriness

Background: Platelet transfusion refractoriness (PTR) is a clinical challenge that can be classified into nonimmunologic and immunologic types, the latter resulting from both platelet alloimmunization and autoimmunity. Recent studies have indicated that platelet clearance can occur without detectable alloantibodies, through mechanisms such as desialylation, apoptosis, and T-lymphocyte dysfunction. In our previous study, platelet desialylation was prevalent in PTR. However, the interplay among desialylation, apoptosis, alloantibodies, and T-lymphocyte dysfunction in platelet clearance remains unclear. Objectives: To elucidate the underlying mechanisms of PTR, focusing on the complex interactions among T-lymphocytes, desialylation, and apoptosis. Methods: RCA-I and Neu1 expression on platelets was measured in patients with PTR and in healthy donors. The capacity of sera from patients with PTR categorized as anti-HLA positive, anti-CD36 positive, or with no detectable antibodies and their corresponding IgG fractions to induce platelet desialylation and apoptosis was assessed. The effects of Fc gamma receptor inhibitors on platelet desialylation and apoptosis were evaluated. T-lymphocyte populations and cytokine levels were investigated. Results: > .05). In PTR, CD4+ T-cell count decreased, CD8+ T-cell count increased, serum interleukin-10 levels increased, and transforming growth factor-β 1 levels decreased. Conclusion: Platelet desialylation, apoptosis, and T-lymphocyte-mediated immune dysregulation jointly contribute to PTR pathogenesis.