Immune thrombocytopenia (ITP) is a bleeding disorder caused by dysregulated B and T cell functions, which lead to platelet destruction. A well-recognised mechanism of ITP pathogenesis involves anti-platelet and anti-megakaryocyte antibodies recognising membrane glycoprotein (GP) complexes, mainly GPIb/IX and GPIIb/IIIa. In addition to the current view of phagocytosis of the opsonised platelets by splenic and hepatic macrophages via their Fc gamma receptors, antibody-induced platelet desialylation and apoptosis have also been reported to contribute to the ITP pathogenesis. Nevertheless, the relationship between the specific thrombocytopenic mechanisms and various types of antiplatelet antibodies has not been established. To ascertain such association, we used sera from 61 ITP patients and assessed the capacity of antiplatelet antibodies to induce neuraminidase 1 (NEU1) surface expression, RCA-1 lectin binding and loss of mitochondrial inner membrane potential on donors’ platelets. Sera from ITP patients with detectable antibodies caused significant platelet desialylation and apoptosis. Anti-GPIIb/IIIa antibodies appeared more capable of causing NEU1 surface translocation while anti-GPIb/IX complex antibodies resulted in a higher degree of platelet apoptosis. In ITP patients with anti-GPIIb/IIIa antibodies, both desialylation and apoptosis were dependent on Fc-gamma RIIa signalling rather than platelet activation. Finally, we confirmed in a murine model of ITP that destruction of human platelets induced by anti-GPIIb/IIIa antibodies can be prevented with the NEU1 inhibitor oseltamivir. A collaborative clinical trial is warranted to investigate the utility of oseltamivir in the treatment of ITP.
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