In this study, by utilizing unique anti-GPIbα and anti-GPIIbIIIa monoclonal antibodies (mAbs) as well as human ITP plasma samples, we show that significant platelet activation and desialylation occurs predominantly in the presence of anti-GPIbα, but not anti-GPIIbIIIa antibodies in vitro and in vivo. The gene discussed is GP1BA; the disease is autoimmune thrombocytopenic purpura.