Dapsone for paediatric chronic immune thrombocytopenia: Short report from a tertiary centre in South India.

Immune thrombocytopenia (ITP) resolves in most children within 3-12 months of diagnosis. Chronic ITP affects 10%-20% of patients, some of whom require treatment. Several second-line agents are efficacious in this group of patients. This paper describes our experience of using dapsone as a single second-line agent in children with chronic ITP. One hundred and three children with chronic ITP were seen at our centre from January 2012 to December 2016. Forty-five children met the inclusion criteria and received dapsone; 17 (37.8%) were boys; and 28 (62.2%) were girls. Early response to dapsone was seen in 37.8% of patients. The median duration of long-term follow-up was 50 months, and at least a partial response was seen in 64.4% of the patients. Dapsone offers good initial response rates and sustained remission in paediatric chronic ITP, comparable to other therapeutic agents available.

Autoimmune cytopenia and Kabuki syndrome in paediatrics: Insights in 11 patients.

Kabuki syndrome (KS) is now listed in the Human Inborn Errors of Immunity (IEI) Classification. It is a rare disease caused by KMT2D and KDM6A variants, dominated by intellectual disability and characteristic facial features. Recurrently, pathogenic variants are identified in those genes in patients examined for autoimmune cytopenia (AIC), but interpretation remains challenging. This study aims to describe the genetic diagnosis and the clinical management of patients with paediatric-onset AIC and KS. Among 11 patients with AIC and KS, all had chronic immune thrombocytopenic purpura, and seven had Evans syndrome. All had other associated immunopathological manifestations, mainly symptomatic hypogammaglobinaemia. They had a median of 8 (5-10) KS-associated manifestations. Pathogenic variants were detected in KMT2D gene without clustering, during the immunological work-up of AIC in three cases, and the clinical strategy to validate them is emphasized. Eight patients received second-line treatments, mainly rituximab and mycophenolate mofetil. With a median follow-up of 17 (2-31) years, 8/10 alive patients still needed treatment for AIC. First-line paediatricians should be able to recognize and confirm KS in children with ITP or multiple AIC, to provide early appropriate clinical management and specific long-term follow-up. The epigenetic immune dysregulation in KS opens exciting new perspectives.

Fatigue, executive function and psychological effects in children with immune thrombocytopenia: a cross-sectional study.

Childhood ITP is often considered to be a relatively mild haematological disorder, with only a minority of patients requiring treatment for troublesome bleeding. Over recent years, wider effects of the condition have been identified in some adults, particularly relating to fatigue and cognitive impairment. In this study, we sought to investigate such effects in a group of children with ITP and further our understanding of their psychological profile. Children attending routine haematology outpatient clinics and their parents were asked to complete standardised questionnaires designed to assess a range of psychological and cognitive factors. Although the majority of children had some scores within the normal range, a significantly high proportion had difficulties with fatigue (70·6%), emotional and behavioural symptoms (25·7%) or executive functioning (19·4%). Quality of life and subjective evaluation of the illness (appraisal) correlated significantly with each of these domains, but bleeding severity and platelet count did not. Our findings provide valuable insight into the broader impact of childhood ITP, which could aid in providing holistic care, potentially contribute to decisions regarding medical treatment, and guide future research.

Patterns and influences in health-related quality of life in children with immune thrombocytopenia: A study from the Dallas ITP Cohort.

BACKGROUND: Relationships between clinical/demographic factors and health-related quality of life (HRQoL) in childhood immune thrombocytopenia (ITP) remain poorly understood. Recent studies reveal conflicting information about factors that contribute to HRQoL. METHODS: This was a prospective, single-institution, cohort study of newly diagnosed children with ITP. Serial evaluations of HRQoL were performed using the Kid's ITP Tools (KIT), scored from 0 (worst) to 100 (best), at enrollment and 1 week, 6 months, and 12 months following diagnosis. All visits included bleeding severity grading. Relationships between HRQoL and platelet count, treatment, bleeding severity, and course of disease were examined. RESULTS: A total of 99 children with newly diagnosed ITP were evaluable for analysis. KIT scores were low at diagnosis for parents (median 26, range 15-43) and children (median 65, range 55-81) and were not influenced by age or platelet count. At diagnosis, children who received treatment had lower platelet counts (P = 0.005), more severe hemorrhage (P < 0.0125), and lower HRQoL by parent, child, and proxy reporting (P < 0.05). Oral bleeding negatively impacted proxy-reported disease burden at diagnosis (P = 0.01). Persistence of disease and lower platelet counts at 6 and 12 month visits were the only factors noted to consistently impact quality of life beyond diagnosis for both parents and children. CONCLUSIONS: HRQoL is low at diagnosis but significantly improves over time. Patients with ongoing disease and lower platelet counts continue to have significant disease burden.

Predictive factors for resolution of childhood immune thrombocytopenia: Experience from a single tertiary center in Thailand.

BACKGROUND: Initial clinical factors that can reliably predict a successful within-1-year resolution of childhood immune thrombocytopenia (ITP) are still unclear. This study aimed to determine factors associated with within-12-month resolution of newly diagnosed childhood ITP. METHODS: The hospital records of 417 consecutive children aged less than 15 years with ITP were reviewed retrospectively and data related to the initial presentation were noted. Logistic regression analysis was used to determine which presenting features were associated with a favorable outcome within 12 months. RESULTS: Significant clinical and laboratory predictors for resolution of newly diagnosed childhood ITP within 12 months were abrupt onset less than 14 days, age less than 5 years, and platelet count at 4 weeks postdiagnosis of at least 100 × 109 l-1 . With these three significant predictors, the rate of within-1-year recovery was more than 97.2%, with a positive predictive value of 97.8% for newly diagnosed childhood ITP. CONCLUSION: Age less than 5 years, onset of bleeding less than 14 days, and follow-up platelet count at 4 weeks of at least 100 × 109 l-1 are significant predictive factors for disease resolution among children with newly diagnosed ITP.

Mycophenolate mofetil for the treatment of children with immune thrombocytopenia and Evans syndrome. A retrospective data review from the Italian association of paediatric haematology/oncology.

Mycophenolate mofetil (MMF) has been shown to be effective in children with immune thrombocytopenia (ITP) and Evans syndrome (ES), but data from larger series and details on the timing of the response are lacking. We evaluated 56 children treated with MMF for ITP (n = 40) or ES (n = 16), which was primary or secondary to autoimmune lymphoproliferative syndrome -related syndrome (ARS). Thirty-five of the 54 evaluable patients (65%) achieved a partial (18%) or complete (46%) response after a median (range) of 20 (7-137) and 37 (7-192) d, respectively. ITP and ES patients responded in 58% and 81% of cases (P = not significant, ns), with complete response in 32% and 81% (P = 0·01), respectively. 60% and 73% of children with primary disease and ARS responded (P = ns) with complete response in 34% and 68% of cases (P = 0·01), respectively. Six of 35 (17%) children relapsed after a median of 283 d (range 189-1036). Limited toxicity was observed in four patients. The median durations of treatment and follow-up were seven and 12·7 months, respectively. This is the largest reported cohort of patients treated with MMF for ITP/ES. The results show that MMF is effective and safe and provides a relatively quick response, suggesting that it has a potential role as an alternative to more aggressive and expensive second/further-line treatments.

Flow cytometric measurement of platelet-associated immunoglobulin in children with newly diagnosed Immune Thrombocytopenia.

OBJECTIVE: To explore the clinical utility of measuring platelet-associated immunoglobulin (PAIG) at the time of diagnosis in children with immune thrombocytopenia (ITP). METHODS: PAIG was measured by flow cytometry using fluorescent murine anti-IgG and anti-IgM. In a cohort of 88 children with ITP, the assay was performed within 15 days of diagnosis and before any treatment in 68 cases. We reviewed the results and examined the relation of isotype profile and degree of elevation to clinical manifestations and course of disease. RESULTS: PAIG was elevated in 74%, with raised IgM being more frequent than IgG (63% vs. 44%, P = 0.04) and with isotype profile depending on symptom onset. Platelet counts at presentation were similar in all subgroups, but mucosal bleeding was less frequent in PAIG-negative patients compared to the positive groups (5.5% vs. 34%, P = 0.03). Duration of thrombocytopenia was similar in negative and positive cases, but during follow-up, significant bleeding events occurred less frequently in PAIG-negative patients (0% vs. 14%, P = 0.18). CONCLUSION: Approximately one-quarter of children are PAIG-negative, and these children have milder bleeding tendency at diagnosis and lower morbidity during follow-up. Raised PAIG possibly may cause some degree of platelet dysfunction.

Diagnosis and Management of Immune Thrombocytopenia in Paediatrics: A Comprehensive Review.

Immune thrombocytopenia (ITP) in paediatric patients is a complex and heterogeneous disorder characterized by isolated thrombocytopenia and an increased risk of bleeding. The diagnosis of ITP involves a careful exclusion of other causes of thrombocytopenia, supported by clinical evaluation and laboratory findings. Management strategies have evolved significantly, emphasizing individualized treatment approaches based on disease severity, bleeding risk, and patient-specific factors. This comprehensive review provides an in-depth analysis of the current diagnostic criteria, including the role of novel biomarkers and genetic testing in distinguishing ITP from other haematological disorders. We also explore the latest therapeutic options, ranging from observation and first-line treatments such as corticosteroids and intravenous immunoglobulin (IVIG) to second-line therapies, including thrombopoietin receptor agonists and immunosuppressive agents. The review addresses the challenges of managing chronic ITP in pediatric patients, focusing on balancing treatment efficacy with the potential side effects and long-term outcomes. Additionally, we discuss the emerging role of personalized medicine in optimizing care for children with ITP, highlighting recent advances in targeted therapies and the potential for future research to refine diagnostic and treatment paradigms to refine diagnostic and treatment paradigms further.

The Ifng antisense RNA 1 (IFNG-AS1) and growth arrest-specific transcript 5 (GAS5) are novel diagnostic and prognostic markers involved in childhood ITP.

Background/aim: IFNG-AS1 is a long noncoding RNA that works as an enhancer for the Interferon-gamma (IFN-γ) transcript. GAS5 (growth arrest-specific 5) is a lncRNA that is associated with glucocorticoid resistance. Aberrant expressions of IFNG-AS1 and GAS5 are directly linked to numerous autoimmune disorders but their levels in childhood ITP are still obscure. This study aims to elucidate expressions of target lncRNAs in childhood ITP and their association with pathophysiology and clinical features of the disease as well as their association with types and treatment responses. Method: The fold changes of target lncRNAs in blood samples from children with ITP and healthy controls were analyzed using quantitative real-time PCR (qRT-PCR). Results: There were overexpressed lncRNAs IFNG-AS1 and GAS5 in serum of childhood ITP patients [(median (IQR) = 3.08 (0.2-22.39) and 4.19 (0.9-16.91) respectively, Also, significant higher IFNG-AS1 and GAS5 (p < 0.05) were present in persistent ITP (3-12 months) [ median (IQR) = 4.58 (0.31-22.39) and 3.77 (0.87-12.36) respectively] or chronic ITP (>12 months) [ median (IQR) = 5.6 (0.25-12.59) and 5.61 (1.15-16.91) respectively] when compared to newly diagnosed <3 months patients [IFNG-AS1 median (IQR) = 1.21 (0.2-8.95), and GAS5 median (IQR) = 1.07 (0.09-3.55)]. Also, significant higher lncRNAs IFNG-AS1 and GAS5 were present in patients with partial response to treatment [IFNG-AS1 median (IQR) = 4.15 (0.94-19.25), and GAS5 (median (IQR) = 4.25 (0.81-16.91)] or non-response [IFNG-AS1 median (IQR) = 4.19 (1.25-22.39) and GAS5 median (IQR) = 5.11 (2.34-15.27)] when compared to patients who completely responded to treatment (IFNG-AS1 median (IQR) = 2.09 (0.2-14.58) and GAS5 (median (IQR) = 2.51 (0.09-10.33). In addition, following therapy, the expressions of IFNG-AS1 and GAS5 are significantly negatively correlated with platelet count. Conclusion: Findings suggest that lncRNAs IFNG-AS1 and GAS5 are novel diagnostic and prognostic genetic markers for childhood ITP that can aid in a precise prediction of the disease's progress at the time of diagnosis and could be a useful tool for treatment planning.

Favorable prognosis of vaccine-associated immune thrombocytopenia in children is correlated with young age at vaccination: Retrospective survey of a nationwide disease registry.

Childhood vaccine-associated immune thrombocytopenia (ITP) has a mostly favorable prognosis. To identify factors associated with prognosis, a retrospective survey was conducted with children with ITP who were registered in the Japanese Society of Pediatric Hematology/Oncology registry from 2008 to 2011. A total of 477 patients were categorized into four groups by event preceding ITP onset: vaccine-precedence (VP; n = 43), vaccine/infection-precedence (VIP; n = 34), infection-precedence (IP; n = 162), and no vaccine/infection-precedence (NVI; n = 238). Compared to IP and NVI, VP and VIP were significantly younger at diagnosis, with the age distribution peaking at infancy, and more frequently had favorable prognosis. Time to platelet recovery to 100 × 103/µL was significantly faster for VP and VIP than NVI. Multivariate Cox regression analysis with sex, age at diagnosis, infection-precedence, and vaccine-precedence as variables revealed age < 36 months (HR 0.992, 95% CI 0.989-0.995; p < 0.001) and male sex (HR 0.770, 95% CI 0.623-0.952; p = 0.015) as associated factors, but not infection-precedence (p = 0.149) or vaccine-precedence (p = 0.650). In subgroup analysis in patients < 36 months, age at diagnosis (p < 0.001) was the only associated factor. Favorable prognosis of childhood vaccine-associated ITP is correlated with young age at vaccination, but not with vaccination itself.

Platelet-specific antibodies and differences in their expression in childhood immune thrombocytopenic purpura predicts clinical progression.

IMPORTANCE: Immune thrombocytopenic purpura (ITP) is the most common bleeding disorder in children. Despite the highly spontaneously remission, still almost 20% of cases progress into chronic or refractory ITP, which seriously affects children's quality of life. Currently there is no method to predict the initial stage of childhood ITP. OBJECTIVES: To evaluate platelet-specific antibodies and compare differences in their expression in childhood ITP to predict clinical progression. METHODS: This is a single-center prospective cohort study from April 2014 to October 2015. We enrolled children initially diagnosed as ITP. Anti-GPIIb/IIIa and GPIb/IX antibodies were assayed by enzyme-linked immunoadsorbent assay (ELISA) and patients were followed up for 1 year. We also analyzed the relationship between the expression of the platelet-specific antibodies GPIIb/IIIa and GPIb/IX and their respective clinical prognoses. RESULTS: Overall, 134 cases were enrolled including 77 boys and 57 girls with a median age of 19 months (range: 1 to 159). Positive rates of anti-platelet antibodies were 79.8%. After a 1-year observation period, 84.3% were diagnosed as newly diagnosed ITP and 13.4% were diagnosed as chronic ITP. Patients with anti-GPIIb/IIIa antibody had a higher risk for newly diagnosed ITP compared with patients who were anti-GPIb/IX antibody positive only (93% vs 25%, P = 0.005; 87% vs 25%, P = 0.014, respectively). There were more anti-GPIb/IX antibody positive only cases, diagnosed as chronic ITP, compared with anti-GPIIb/IIIa antibody positive only cases and double GPIIb/IIIa and GPIb/IX antibody positive cases (75% vs 7%, P = 0.005; 75% vs 13%, P = 0.014, respectively). Interpretation. INTERPRETATION: Patients with anti-GPIIb/IIIa antibody (either single or double) were predicted to have a good prognosis, whereas anti-GPIb/ IX antibody only predicted a poor prognosis. These results should be confirmed via a larger cohort multicenter study.

Childhood immune thrombocytopenia: Clinical presentation and management.

Immune thrombocytopenia (ITP) is an acquired hematological disorder that is developed secondary to the production of auto-antibodies against platelets leading to isolated thrombocytopenia, in the absence of other causes of thrombocytopenia such as drugs, infections, malignancy, or other autoimmune diseases [1-6]. ITP commonly affects children between one and seven years of age. Severe life threatening bleeding is rare (0.2-0.9%) [7-12]. Childhood primary ITP usually runs a benign, self-limiting course, with or without treatment. Complete remission occurs within six months from diagnosis, commonly within 6-12 weeks, in the majority of children with the diagnosis of ITP. However, 20-30% of children will continue to have persistent low platelets count with bleeding symptoms beyond six months from diagnosis [4, 12-18]. The diagnosis of ITP in children is essentially one of exclusion. The child is usually one to seven years old, develops skin bruises, petechiae, or mucosal bleeding, who is otherwise healthy and having no lymphadenopathy or organomegally. Full blood count reveals isolated thrombocytopenia with normal hemoglobin (Hb) level, white blood count (WBC) and normal peripheral blood smear. Initial management options for newly diagnosed childhood ITP include; observation only, the use of intravenous immunoglobulin (IVIG), steroids, anti-D immunoglobulin, each alone or in combination [6, 19.] Children who develop chronic ITP may benefit from splenectomy [19, 20-24]. Rituximab, a chimeric monoclonal antibody (anti-CD20), may lead to complete remission, and defers the need for splenectomy [25-27]. Recently, the thrombopoietin (TPO) agonists (Romiplostim and Eltrombopag) produced very good response in adult and pediatric patients with severe chronic ITP [28-30].