Pathophysiology and clinical challenges of childhood immune thrombocytopenia and future directions

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease that causes thrombocytopenia due to platelet destruction and impaired platelet production. Pathological triggers such as viral infections induce the presentation of cryptic peptides derived from platelet antigens from antigen-presenting cells to CD4⁺ T cells, resulting in anti-platelet autoantibody production in B cells. There are five established treatment options for childhood ITP: high-dose gamma globulin therapy, corticosteroids, thrombopoietin receptor agonists, rituximab, and splenectomy. The underlying pathophysiology of ITP helps in elucidating the site of action of each drug. Many children with ITP undergo remission spontaneously. However, the following issues arise: (1) selection criteria for patients to be treated, (2) selection of initial treatment, (3) treatment of refractory patients, (4) treatment selection considering patient/family health-related quality of life (HRQoL), and (5) clinical positioning of splenectomy after introduction of new drugs. In Europe and the United States, treatment is selected on the basis of the severity of bleeding symptoms regardless of the platelet count. Buchanan’s bleeding grade is often used to assess the severity of bleeding. Conventionally, patients with the Buchanan classification Grades 0 to 2 are carefully monitored, whereas those with and Grades 4 and 5 should be treated. Whether or not to treat patients with Grade 3 classification is an issue for consideration. We are in an era where treatments that improve the patient’s HRQoL can be selected instead of patients adjusting their lifestyle on the basis of their platelet count. In this paper, an overview of the pathophysiology of childhood ITP, clinical issues, the American Society of Hematology (ASH) 2019 ITP guidelines, and treatment of chronic ITP are presented.