Post-transfusion purpura: pathogenic mechanisms and relationship with immune thrombocytopenia: a critical analytical...

Post-transfusion purpura (PTP) is a rare, life-threatening immune-mediated adverse transfusion event. It is characterized by severe thrombocytopenia developing 5-10 days after transfusion of platelet-containing blood products. The most notable pathological paradox is that alloantibodies directed against foreign human platelet antigen (HPA) can destroy the patient's autologous platelets that do not express the corresponding target antigen. PTP predominantly affects middle-aged women, and its major clinical manifestation is mucocutaneous bleeding, with intracranial hemorrhage being the leading cause of death. The disorder is mostly self-limiting, and three major hypotheses have been proposed to explain its pathogenesis: immune-complex-mediated injury, antigen adsorption, and concomitant autoantibody production. Evidence from clinical serological assays, recombinant autoantibody studies and animal models suggests that B-cell somatic hypermutation drives the transition from alloimmunity to transient autoimmunity with the generation of anti-platelet autoantibodies, which constitutes the core pathogenic mechanism of PTP. By contrast, the immune-complex pathway and antigen-adsorption mechanism likely exert auxiliary and synergistic effects, without sufficient in-vivo human evidence to validate them. PTP shares certain similarities while exhibiting marked distinctions from immune thrombocytopenia (ITP). Pathogenic antibodies in both conditions target conserved epitopes on platelet glycoproteins. Nevertheless, PTP is initiated by memory-B-cell-mediated anamnestic alloimmunity, with transient autoantibodies and mostly spontaneous clinical resolution. ITP, by comparison, represents a chronic primary autoimmune disorder with persistently circulating autoantibodies that frequently require long-term immunosuppressive therapy. Single-cell multi-omics technologies hold promise for deciphering the clonal relationship between alloantibody-secreting and autoantibody-secreting B cells, elucidating the transient autoimmune cascade underlying PTP, and offering novel therapeutic targets for dissecting immune tolerance breakdown and treating refractory antibody-mediated autoimmune hematological diseases including ITP.