title: The ITP syndrome: pathogenic and clinical diversity.
abstract: Immune thrombocytopenia (ITP) is mediated by platelet autoantibodies that accelerate platelet destruction and inhibit their production. Most cases are considered idiopathic, whereas others are secondary to coexisting conditions. Insights from secondary forms suggest that the proclivity to develop platelet-reactive antibodies arises through diverse mechanisms. Variability in natural history and response to therapy suggests that primary ITP is also heterogeneous. Certain cases may be secondary to persistent, sometimes inapparent, infections, accompanied by coexisting antibodies that influence outcome. Alternatively, underlying immune deficiencies may emerge. In addition, environmental and genetic factors may impact platelet turnover, propensity to bleed, and response to ITP-directed therapy. We review the pathophysiology of several common secondary forms of ITP. We suggest that primary ITP is also best thought of as an autoimmune syndrome. Better understanding of pathogenesis and tolerance checkpoint defects leading to autoantibody formation may facilitate patient-specific approaches to diagnosis and management.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, 513A Stellar-Chance, 422 Curie Blvd, Philadelphia, PA 19104, USA. dcines@mail.med.upenn.edu
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cines
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.forename: Howard A
authors.initials: HA
authors.lastname: Liebman
authors.forename: Eline T
authors.initials: ET
authors.lastname: Luning Prak
mesh_terms: D000328:Adult; D016824:Antigens, Human Platelet / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology; D002648:Child; D003141:Communicable Diseases / Q000150:complications / Q000276:immunology; D004198:Disease Susceptibility; D019337:Hematologic Neoplasms / Q000150:complications / Q000276:immunology; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D015994:Incidence; D016131:Lymphocyte Subsets / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D017634:Self Tolerance / Q000276:immunology; D034061:Thrombopoiesis; D014181:Transplantation Immunology; D014611:Vaccination / Q000009:adverse effects
chemical_list: D016824:Antigens, Human Platelet; D001323:Autoantibodies