title: Novel treatments for immune thrombocytopenia.
abstract: Primary immune thrombocytopenia (ITP) is caused by platelet autoantibodies and T-cell dysregulation. Both platelets and their precursor megakaryocytes may be targeted leading to platelet destruction and underproduction. Current treatments for ITP are inadequate since they do not reverse the disease process and generally do not result in durable remissions. In addition, many treatments are limited by side effects including infection and potentially thrombosis. Novel agents that are currently in development target certain key steps in the disease process, including: (1) the interaction between T-cell and antigen presenting cells (CD40-CD154 interaction); (2) the binding of the Fc portion of platelet autoantibodies to Fc-receptors on macrophages (soluble Fc-RIIb); and (3) the signaling pathways leading to platelet phagocytosis by macrophages (Syk inhibition). Other strategies have been to augment platelet production by simulating thrombopoiesis or by neutralizing physiological inhibitors of megakaryopoiesis. Targeted therapies in ITP have the potential to improve disease morbidity and mortality while limiting systemic side effects. Before these agents can be used in practice, additional clinical studies are needed with rational study outcomes including platelet count, bleeding and quality of life. An individualized treatment strategy is needed for patients since ITP is a distinctly heterogeneous disease.
authors.affiliation: McMaster University, Department of Medicine, Hamilton, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Shih
authors.affiliation: McMaster University, Department of Medicine, Hamilton, Ontario, Canada.
authors.forename: Ishac
authors.initials: I
authors.lastname: Nazi
authors.affiliation: McMaster University, Department of Medicine, Hamilton, Ontario, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Kelton
authors.affiliation: McMaster University, Department of Medicine, Hamilton, Ontario, Canada; Canadian Blood Services, Hamilton, Ontario, Canada. Electronic address: arnold@mcmaster.ca.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Arnold
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D001323:Autoantibodies / Q000627:therapeutic use; D001792:Blood Platelets / Q000276:immunology; D019013:CD40 Antigens; D023201:CD40 Ligand / Q000627:therapeutic use; D006801:Humans; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D019013:CD40 Antigens; D023201:CD40 Ligand