title: Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production.
abstract: Chronic immune thrombocytopenia (ITP) is a haematological disorder in which patients predominantly develop skin and mucosal bleeding. Early studies suggested ITP was primarily due to immune-mediated peripheral platelet destruction. However, increasing evidence indicates that an additional component of this disorder is immune-mediated decreased platelet production that cannot keep pace with platelet destruction. Evidence for increased platelet destruction is thrombocytopenia following ITP plasma infusions in normal subjects, in vitro platelet phagocytosis, and decreased platelet survivals in ITP patients that respond to therapies that prevent in vivo platelet phagocytosis; e.g., intravenous immunoglobulin G, anti-D, corticosteroids, and splenectomy. The cause of platelet destruction in most ITP patients appears to be autoantibody-mediated. However, cytotoxic T lymphocyte-mediated platelet (and possibly megakaryocyte) lysis, may also be important. Studies supporting suppressed platelet production include: reduced platelet turnover in over 80% of ITP patients, morphological evidence of megakaryocyte damage, autoantibody-induced suppression of in vitro megakaryocytopoiesis, and increased platelet counts in most ITP patients following treatment with thrombopoietin receptor agonists. This review summarizes data that indicates that the pathogenesis of chronic ITP may be due to both immune-mediated platelet destruction and/or suppressed platelet production. The relative importance of these two mechanisms undoubtedly varies among patients.
authors.affiliation: Department of Hematology, Children's Hospital of Orange County, Orange, CA, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Nugent
authors.forename: Robert
authors.initials: R
authors.lastname: McMillan
authors.forename: Janet L
authors.initials: JL
authors.lastname: Nichol
authors.forename: Sherrill J
authors.initials: SJ
authors.lastname: Slichter
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001792:Blood Platelets / Q000276:immunology / Q000473:pathology*; D002908:Chronic Disease; D006801:Humans; D010976:Platelet Count; D013921:Thrombocytopenia / Q000276:immunology / Q000473:pathology*; D034061:Thrombopoiesis / Q000276:immunology; D013926:Thrombopoietin / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D013926:Thrombopoietin