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.