Immune thrombocytopenia (ITP) is a common bleeding disorder caused primarily by autoantibodies against platelet GPIIbIIIa and/or the GPIb complex. Current theory suggests antibody-mediated platelet destruction occurs in the spleen via Fcγ receptors (FcγR). However, it has been demonstrated that anti-GPIbα-mediated ITP is often refractory to therapies targeting FcγR pathways. Utilizing a panel of murine monoclonal antibodies (mAbs) against murine and human GPIIbIIIa and GPIbα, it was found that anti-GPIbα induces not only platelet activation to a much greater extent than anti-GPIIbIIIa antibodies, but also significant surface expression of neuraminidase 1 and platelet desialylation. Utilizing inhibitors of platelet activation and desialylation, it was found that these two processes are not mutually exclusive, but rather exist in a positive feedback loop, leading to FcγR-independent platelet clearance in the liver likely via Ashwell-Morell receptors. Furthermore, in a murine model of ITP, sialidase inhibitor treatment rescued platelet counts in predominantly anti-GPIbα -mediated thrombocytopenia.

Immune thrombocytopenia (ITP) is a common bleeding disorder caused primarily by autoantibodies against platelet GPIIbIIIa and/or the GPIb complex. Current theory suggests antibody-mediated platelet destruction occurs in the spleen via Fcγ receptors (FcγR). However, it has been demonstrated that anti-GPIbα-mediated ITP is often refractory to therapies targeting FcγR pathways. Utilizing a panel of murine monoclonal antibodies (mAbs) against murine and human GPIIbIIIa and GPIbα, it was found that anti-GPIbα induces not only platelet activation to a much greater extent than anti-GPIIbIIIa antibodies, but also significant surface expression of neuraminidase 1 and platelet desialylation. Utilizing inhibitors of platelet activation and desialylation, it was found that these two processes are not mutually exclusive, but rather exist in a positive feedback loop, leading to FcγR-independent platelet clearance in the liver likely via Ashwell-Morell receptors. Furthermore, in a murine model of ITP, sialidase inhibitor treatment rescued platelet counts in predominantly anti-GPIbα -mediated thrombocytopenia.