Immune thrombocytopenia is an autoimmune disease predominantly caused by autoantibody mediated platelet and megakaryocyte destruction and or dysfunction, which leads to low platelet counts and risk of bleeding. Currently prognostic biomarkers are underdeveloped and there lacks a gold-standard for therapeutics, which leaves an inexplicable refractory subset of patients which are clinically challenging. Autoantibodies in ITP predominantly target the two most abundantly expressed platelet surface antigens integrin GPIIbIIIa and GPIb-IX. We and others have reported antibodies against GPIbα tend to exhibit more refractoriness to common ITP therapies such as steroids and intravenous IgG (IVIG). Here we discuss the mechanisms which could contribute to the increased resistance, including our recent finding of anti-GPIbα-, and some anti-GPIIbIIIa- mediated platelet activation and desialylation, leading to Fc-independent platelet clearance. Furthermore, we discuss the emerging clinical investigations of utilizing desialylation as a biomarker/prognostic tool in identifying the refractory subset, as well as the therapeutic benefits of targeting desialylation with sialidase inhibitors.

Immune thrombocytopenia, Autoantibodies, Platelets, GPIbα, Integrin