Relationship between pathogenic mechanisms and clinical responses in ITP. The pathogenesis of ITP involves multiple aspects of immune dysregulation, involving several types of cells (B and T lymphocytes, dendritic cells, plasma cells) and resulting in both shortened platelet survival and inhibition of platelet production. In theory, the pathogenesis of childhood ITP or ITP that follows viral infections is less complex, and affects primarily peripheral tolerance. This form of ITP responds more readily to therapy or may remit spontaneously. In contrast, the pathogenesis of ITP in which there is a differentiation block or loss of central tolerance, such as in patients with neoplasia or autoimmune disease, is poorly understood and multifaceted, making therapy of such individuals more difficult. In such cases, combination therapy targeting more than 1 arm of the maladaptive immune response may be effective. ALPS, autoimmune lymphoproliferative syndrome; APS, antiphospholipid syndrome; CLL, chronic lymphocytic leukemia; CMV, cytomegalovirus; Evans, Evans syndrome; H pylori, Helicobacter pylori; IST, immunosuppressive therapy; SLE, systemic lupus erythematosus; VZV, varicella-zoster virus. Professional illustration by Patrick Lane, ScEYEnce Studios.