Refractory idiopathic immune thrombocytopenic purpura in children: current and future treatment options.

A minority of children with idiopathic or immune thrombocytopenic purpura (ITP) have the refractory chronic form with bleeding problems (stage III or IV). The aim of this article is to provide an update on the immunopathogenesis and management of children with bleeding and severe refractory ITP. The management of such patients, according to a staging guideline, is described. Recent clinical and laboratory observations document the disturbed immune responses that occur on various levels in chronic ITP. New therapeutic options are directed towards influencing these immunopathogenic mechanisms. Because ITP is not adequately defined and has heterogeneous manifestations, today's management recommendations are largely opinion-based rather than evidence-based. In severe refractory childhood ITP, consensus between the treating physician and the patient has to be achieved on an individual basis. The aim is to maintain the disease at stages I or II, with minimal intervention, and to prevent bleeding. If bleeding is not under control, medical treatment (as described in this article), or splenectomy, has to be considered.Although there is a paucity of data relating to children, potential new treatment options for refractory ITP include strategies aimed at influencing antigenemia, the T cell immune response (e.g. cyclosporine, CTLA-4-Ig) or the B-cell immune response (e.g. anti-CD20 monoclonal antibody, anti-CD52 monoclonal antibody, interferon). New prospective, cooperative ITP registries have been created to search for subgroups with different severities of ITP, which will be the selection criteria of future controlled studies in pediatric patients with refractory ITP.