Immune thrombocytopenia (ITP) can look quite different depending on the person’s age. This research study focuses on how ITP can affect infants and toddlers differently.
Researchers looked at 52 children with ITP followed at one hospital over a 13-year period: 22 were infants (1-12 months old) and 30 were toddlers (13-47 months old) at the time of diagnosis. The factors that were investigated were platelet count at diagnosis, lowest-ever platelet count, treatments, duration of ITP, bleeding, and vaccinations.
It was found that bleeding severity, the platelet count at diagnosis, the lowest-ever platelet count recorded, and the proportion of those receiving medication treatment were quite similar when comparing infants and toddlers. More infants had a vaccine in the 6 weeks prior to the diagnosis of ITP compared to toddlers (13/22 vs 1/30).
Infants went into remission more rapidly than toddlers (1.9 months vs. 4.9 months). Significantly fewer infants (1/22) developed chronic ITP (lasting longer than 12 months) compared to toddlers (9/30).
Out of the 22 infants with ITP, 15 did not require any medication treatment and 7 received either IVIG or steroids. Additionally, the bleeding severity was either minor or mild in 19/22 of the infant population. The one infant who developed chronic ITP received IVIG and steroids and then received eltrombopag for 12 months, which led to good quality of life and control of bleeding.
Comments from PDSA Medical Advisors
This study is one of a very small number that explores ITP in toddlers and young infants. Historically, clinicians and families worried that a diagnosis of ITP before one year of age may be associated with a higher rate of underlying immune issues or worse outcomes. This report demonstrates that children in both these age groups have a high rate of spontaneous remission, and many have no or mild bleeding symptoms and can often be closely observed up until the time of remission. Due to the small numbers looked at in this study, in addition to the very small numbers of studies looking at ITP in these age groups, it is not possible to make strong conclusions about ITP in toddlers and infants other than to infer the study shifts the balance a little towards ‘better outcome.’
Currently, both the American Society of Hematology and the International Working Group use the term “refractory” when a patient with immune thrombocytopenia (ITP) continues to have ITP despite having had a splenectomy. However, splenectomy is uncommon, especially in the pediatric population. Therefore, this study looked through existing research papers to find how others have defined the term ‘refractory’ and the effect of treatment in this population. The goal was to work towards finding a more practical standardized definition of refractory ITP, which could harmonize future research studies and treatment suggestions. The researchers also gathered the opinions of ITP experts to further understand how they define refractory ITP.
The investigators identified 11 relevant research papers that discussed the definition of refractory ITP in children. To highlight the inconsistency in the use of the term, even among researchers, of these 11 papers, patient history was used to help define refractory ITP in seven, an analysis of cells in the blood (referred to as a ‘complete blood count’) was used in three, the risk of bleeding was also used by three, and response to splenectomy was used by one paper.
In addition, some of the above-mentioned papers defined refractory ITP by the patient’s lack of response to therapies like splenectomy, steroids, IVIG, cyclosporine, rituximab, and/or mycophenolate mofetil (MMF). Some research papers stated that ITP is considered refractory when there is an increased bleeding risk that requires frequent medication. Two research papers required that platelet counts be less than 30,000/µl to be considered refractory ITP, and one paper required the platelet count to be less than 20,000.
When surveyed, 55% of pediatric ITP experts thought children with ITP who did not respond to an initial second-line therapy were refractory. Patients with chronic ITP (having ITP for more than a year) who did not respond well to IVIG and had no response to thrombopoietin receptor agonists (eltrombopag [Promacta®/Revolade®] or romiplostim [Nplate®]) were considered to have refractory disease by 96% of the experts. Patients with newly diagnosed ITP who did not respond to steroids, IVIG, or thrombopoietin receptor agonists and required platelet transfusions for bleeding were also considered refractory by 85% of experts. Lastly, 75% said that a temporary response to IVIG was not enough to categorize someone as having refractory ITP.
Out of the 11 research papers reviewed in this study, eight discussed treatment options for children with refractory ITP, which included splenectomy, rituximab, romiplostim, and dapsone. The most discussed treatment option was rituximab.
Comments from PDSA Medical Advisors
Clinicians and researchers do not currently agree on a definition of refractory ITP. Creating a standard definition for refractory ITP would improve consistency between research studies and understanding results from clinical trials. A standard definition for refractory ITP would also help researchers to understand if the underlying biology of ITP is different in those with refractory ITP versus those with ITP that is more typical. This understanding could help improve the treatment approach in this patient population. A series of research papers in the British Journal of Hematology will be published later this year, addressing current understandings of refractory ITP from multiple viewpoints.