Introduction
Pediatric immune thrombocytopenia (ITP) is an acquired autoimmune disorder caused by destruction of platelets and impairment of platelet production which manifests as isolated thrombocytopenia and variable bleeding symptoms in children.1 ITP can be classified based on disease duration and includes newly diagnosed (0-3 months), persistent (3-12 months), and chronic (>12 months).2 Evidence-based ITP guidelines and an international consensus report recommend frontline therapy for patients with newly diagnosed ITP to include observation, corticosteroids, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin.1,2 Spontaneous remission has been reported in more than 50% of pediatric patients.3Patients with significant bleeding symptoms may undergo additional treatment with either an additional first-line therapy, initiation of thrombopoietin receptor agonists (TPO-RA), rituximab, other immunosuppressant therapy, or splenectomy. The goals of acute treatment are to control active bleeding, improve quality of life, and minimize adverse events, irrespective of platelet count.4
Data exist to guide the development of diagnostic and therapeutic approaches for patients with newly diagnosed, persistent, and chronic ITP. Some children will have a poor or transient response to ITP-directed treatments and are referred to as refractory ITP (rITP). An International Working Group defined a group of patients as having rITP if they met two criteria: (1) they failed splenectomy and (2) they either continued to have severe ITP or a risk of bleeding requiring treatment. The 2011 American Society of Hematology (ASH) guidelines also defined rITP as having severe ITP that persisted after splenectomy. However, few pediatric patients undergo splenectomy. As such, the above rITP definition would exclude the majority of challenging pediatric patients. Some children with ITP do not respond or have only a transient response to multiple first and or second-line therapies. These patients are subject to ongoing bleeding risk, and consequently, patients’ estimated life expectancy and quality-adjusted life expectancy are severely compromised.5 In addition to the drawbacks of the current pediatric rITP definitions, there are also no evidence-based guidelines to support treatment approaches in this patient population.
The ITP Consortium of North America (ICON) identified a critical need to examine the current definitions of rITP in children used in the medical literature and in clinical practice. An ICON working group performed a systematic review of the literature to examine current use of the term rITP and surveyed ICON members on clinical use of the term rITP. Based on these findings, the authors propose an updated definition as the first step in developing standardized treatment recommendations for pediatric rITP.