Childhood Immune Thrombocytopenia Research Articles

Case Report: MYH9-related disease caused by Ala44Pro mutation in a child with a previous diagnosis of chronic immune thrombocytopenia

MYH9-related disease, a rare autosomal dominant platelet disorder characterized by thrombocytopenia, giant platelets, and leukocyte inclusion bodies, may mimic immune thrombocytopenia in children unless suspected and carefully excluded. Here, we present a case involving a three-year-old girl with mild bleeding symptoms since infancy, previously diagnosed with chronic immune thrombocytopenia. The patient exhibited isolated thrombocytopenia and lacked any family history of thrombocytopenia, hearing impairment, or renal failure. Examination of peripheral blood smears via light microscopy revealed significant platelet macrocytosis with giant platelets and basophilic Döhle-like bodies in the neutrophils. Subsequent sequencing analysis of MYH9 gene identified a p.Ala44Pro mutation. Throughout a six-year follow-up period, the patient's condition remained stable. Our report underscores the significance of identifying leukocyte inclusion bodies in peripheral blood smears and considering MYH9-related diseases, even in instances of chronic macrothrombocytopenia devoid of familial history or non-hematological manifestations.

Results of treatment of patients with newly diagnosed immune thrombocytopenia: is it justified to follow clinical recommendations?

Immune thrombocytopenia (ITP) is an acquired immune-mediated disease characterized by isolated transient or persistent thrombocytopenia < 100·109/L. The incidence of immune thrombocytopenia is 4–6,4 per 105 children/year.Purpose. To analyze the results of treatment newly diagnosed immune thrombocytopenia according to the clinical guidelines (ID699) published on the website of the Ministry of Health of Russia.Material and methods. The analysis included 13 patients (F–46%, M–54%, median age — 9.5 (4–17) years) with immune thrombocytopenia admitted to the Tver Regional children hospital in 2023. A history of infection preceding the immune thrombocytopenia was in 69% of cases and measles vaccination in 8%. The median period from the onset of infection was 11 (5–15) days. Degree of bleeding was — 1 gr. — 4 (31%), 2 gr. — 3 (23%), 3 gr. — 6 (46%). Hematuria was observed in 3 (23%), menorrhagia in 1 (8%) case. The mean platelet count at the time of admission was 9,0 (1.0–86) · 109/l.Results. The incidence was 5.7 per 105 children/year. Dexamethasone 20 mg/m2, days 1–3, was used in 54% of cases; IVIG 1000 mg/kg, day 1 in 15%, prednisolone 2 mg/kg, day 21 in 8% and in 23% of cases dynamic follow-up was performed. In 2 cases (17%), discontinuation of steroid therapy and switching to IVIG was required due to a hemorrhagic syndrome deterioration or/and complication of steroid therapy. Partial and complete responses were achieved in 8 (62%) and 4 (31%) cases respectively. In 1 (8%) case, the response could not be evaluated. The summary efficacy of first-line therapy was 92%.Conclusion. The clinical guidelines ID699 was highly effective in achieving a primary response and preventing recurrence of immune thrombocytopenia in children.

Recommendations for the management of acute immune thrombocytopenia in children. A Consensus Conference from the Italian Association of Pediatric Hematology and Oncology.

Immune thrombocytopenia (ITP) is an acquired immune-mediated bleeding disorder characterized by isolated thrombocytopenia. Its estimated yearly incidence in the pediatric population is 1.9-6.4/100,000. ITP in children is usually a self-limiting and benign disorder. The clinical management of children with ITP often remains controversial, as robust randomized trials on the management of this disorder are lacking. Treatments vary widely in clinical practice and existing guidelines from hematology societies on clinical management offer indications based largely on expert opinion rather than strong evidence. The Coagulative Disorder Working Group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) developed this document to collect shared expert opinions on the management of newly diagnosed ITP, updating previous guidelines and providing recommendations to pediatricians. Each statement has been given a score expressing the strength of evidence, appropriateness and agreement among participants. Clear-cut definitions of the clinical phases of the disease and clinical response are stated. Recommendations are given regarding the classification of bleeding symptoms, evaluation of bleeding risk, diagnosis, and prognostic factors. Specific recommendations for treatment include indications for first-line (intravenous immunoglobulins, steroids) and second-line (combined therapy, thrombopoietin receptor agonists, immunosuppressive drugs, rituximab) therapeutic agents, as well as hemorrhagic emergency and supportive treatment, including emergency splenectomy. The optimal follow-up schedule, the relation between ITP and vaccines and health-related quality-of-life issues are also discussed. The panel achieved broad consensus on issues related to how to treat children with newly diagnosed ITP, providing a comprehensive review of all relevant clinical aspects.

Novel Perspectives on Thrombopoietin Receptor Agonists Applications.

Second-generation thrombopoietin receptor agonists (TPO-RAs), romiplostim, eltrombopag, and avatrombopag, have been proved to be significant stimulators of megakaryopoiesis and, in the last decade, they have been incorporated in the treatment options against refractory immune thrombocytopenia in children and adults that do not respond to conventional therapy. Additionally, given their beneficial impact on hematopoiesis, they have successfully been applied in cases of non-immune thrombocytopenia, such as aplastic anemia, HCV-related thrombocytopenia, chronic liver disease, and most recently acute radiation syndrome. During the past years, a wide variety of clinical studies have been performed, in regard to the use of TPO-RAs in various thrombocytopenic settings, such as malignant hematology and hematopoietic stem cell transplantation, hereditary thrombocytopenias, and chemotherapy-treated patients with solid organ tumors. Although data indicate that TPO-RAs may be an effective and safe option for managing disease- or treatment-related thrombocytopenia in these patients, further research is needed to determine their efficacy and safety in these settings. Furthermore, recent studies have highlighted novel properties of TPO-RAs that render them as potential treatment candidates for reducing tumor burden or fighting infections. Herein, we discuss the potential novel applications of TPO-RAs and focus on data regarding their efficacy and safety in these contexts.

Expression of MicroRNA-3162-3p in Different Clinical Stages of Children with Primary Immune Thrombocytopenia and Its Significance

To explore the expression of microRNA-3162-3p in different clinical stages of childhood primary immune thrombocytopenia (ITP) and its significance. Ninety-six children with ITP were enrolled and divided into new diagnosis group (n=40), persistent group (n=30) and chronic group (n=26) according to the course of disease. 80 healthy children were selected as the control group. Peripheral blood mononuclear cells (PBMNC) of ITP children and healthy children were isolated and cultured, and the expression of microRNA-3162-3p in PBMNC of subjects was detected by real-time fluorescence quantitative PCR. The contents of IL-17, IL-23, IL-10 and TGF-β in PBMNC of subjects were determined by ELISA. The correlation between microRNA-3162-3p and platelet count, IL-17, IL-23, IL-10 and TGF-β was analyzed. Compared with the control group, the expression of microRNA-3162-3p and IL-10 in PBMNC and platelet count of ITP children were significantly decreased（P < 0.05）, while IL-17, IL-23 and TGF-β were significantly increased (P < 0.05). With the prolongation of the disease course, the expressions of microRNA-3162-3p and IL-10 in PBMNC and platelet count were significantly decreased（P < 0.05）, while the expressions of IL-17, IL-23 and TGF-β were significantly increased (P < 0.05). The expression of microRNA-3162-3p in PBMNC was positively correlated with platelet count and IL-10 (r =0.716, 0.667), and negatively correlated with IL-17, IL-23, and TGF-β (r =-0.540, -0.641, -0.560). MicroRNA-3162-3p expression is significantly reduced in PBMNC of children with ITP, and is involved in the regulation of Th17/Treg imbalance, which can be used as a potential therapeutic target of ITP.

Immune Thrombocytopenia in Children

Immune thrombocytopenia is a hematological disorder defined by an isolated decrease in platelet numbers. We present a retrospective-descriptive study that enrolls twenty-five children (aged 0-18 years old) admitted to Brasov Children’s Hospital from the 1st of January 2020 until the 1st of September 2023 with the diagnosis of idiopathic thrombocytopenic purpura (ITP).&#x0D; We could find proof of recent viral infection in seven patients out of twenty-five; three of them also had immunological findings- positive antinuclear, positive direct Coombs test, or antiplatelet antibodies. The medical literature mentions glucocorticoids and IVIG therapy as the first line of treatment for immune thrombocytopenic purpura, while new pharmaceutical agents are still under review.

Assessment of Clinical and Laboratory Predictors for Chronic Childhood Immune Thrombocytopenia

Assessment of Clinical and Laboratory Predictors for Chronic Childhood Immune Thrombocytopenia

ITGB1-Expressing Effector Memory CD4 + T-Cell Response Associates with Clinical Recovery in Childhood Immune Thrombocytopenia

Background: The autoimmune bleeding disorder childhood immune thrombocytopenia (ITP) features antibody and T-cell immune responses against platelet self-antigens. This involves activation of B-cells, CD4 + T-cell help, and CD8 + T-cells. Novel prognostic biomarkers are needed to predict recovery and treatment responses. Compared to healthy children, changes in total lymphocytes, CD4 +, regulatory CD4 +, CD8 +T-cells, CD19 + B-cells, and NK cells were described in childhood ITP. Children with transient ITP were also found to have a fewer CD25 hi CD4 + T-cells than those who develop chronic ITP. In contrast, the platelet-stimulated peripheral blood mononuclear cells (PBMC) of children with chronic ITP produced more IL-2 than those of transient ITP. At present, none of these biomarkers have been validated for ITP prognosis, and consequently they are not in clinical use. This emphasizes the need for clinical-grade biomarkers to predict clinical responses in childhood ITP. Aims: To predict spontaneous recovery and IVIg response in newly diagnosed ITP by (1) validating previously suggested changes in immune cell frequencies, and (2) identifying novel immune cell subsets as predictors. Methods: Children with newly diagnosed ITP were randomized 1:1 to observation or IVIg treatment (TIKI trial). Recovery was determined by platelet counts according to IWG criteria 1, 4, 13, 26 and 52 weeks after the diagnosis. For validation, the CD4 +, regulatory CD4 + (CD25 +/CD127 lo), CD8 +, CD19 +, and NK cells were quantified at the time of diagnosis in a centralized laboratory by flow cytometry. For identification of novel predictors, CD4 + central (CD45RO + CD27 +) and effector memory (CD45RO + CD27 -) frequencies were determined. The primary clinical outcome was longitudinal recovery, either spontaneous or after IVIg (adjusted Cox-proportional hazard model). Secondary outcomes included the mean age-adjusted difference between transient/persistent and chronic ITP by multivariate regression, and comparison to age-appropriate healthy control data. Additionally, PBMC (N=6) were analyzed at diagnosis by single-cell RNA sequencing (scRNA-seq) combined with T- and B- cell receptor sequencing (scTCR-seq and scBCR-seq). Results: For validation of previously suggested predictors, the absolute CD3 +, CD4 +, CD8 +, CD19 +, and NK cell counts of newly diagnosed ITP patients were within the age-appropriate healthy reference range (N=158); they were not associated with recovery, and there were no age-adjusted differences between transient/persistent (N=139) and chronic ITP (N=19). The regulatory CD4 + T cell frequency was not reduced compared to age-appropriate reference data; not associated with recovery, and not different between transient/persistent and chronic ITP patients. For identification of novel predictors, we found that high CD4 +effector memory cells numbers were associated with a reduced recovery rate, with an adjusted hazard ratio for complete recovery over a one-year follow-up to be 0.55 (95% CI, 0.35 - 0.85; ≥ median; adjusted for age and treatment; N=150). Chronic ITP patients displayed a mean age-adjusted increase in effector memory CD4 +cells of 1.4 % (95% CI, 0.4 - 2.4; P= 0.005). The association with recovery was independent of a preceding infection, total leukocyte and lymphocyte counts, and the presence of anti-platelet IgG or IgM autoantibodies. ScRNA-seq analysis of 7965 PBMC also showed an effector memory CD4 + T-cell cluster that was expanded in chronic ITP, present in at a frequency of 8.1 ± 1.4 % (mean ± sem) in transient vs 14.8 ± 1.2 % in chronic ITP. This cluster also expressed high levels of fibronectin receptor integrin b1 ( ITGB1) interleukin 32 (IL32) interleukin 7 receptor (IL7R) andlymphotoxin beta (LTB). The effector memory phenotype of CD4 + ITGB1 + T-cells was confirmed by flow cytometry analysis in healthy individuals and ITP patients. Conclusions: Previously suggested changes in T-, B-, or NK cell frequencies could not be validated as predictors of spontaneous recovery or IVIg response. However, we identified the frequency of ITGB1-expressing effector memory CD4 + T cells as an independent predictor of spontaneous recovery and IVIg response. Thus, T cell phenotyping at the time of diagnosis may be suitable to determine prognosis and personalize treatment decisions in newly diagnosed childhood ITP.

A Phase 3 Study of Eltrombopag Vs. Standard First-Line Management for Newly Diagnosed Immune Thrombocytopenia in Children: Trial in Progress Update

Background: Immune thrombocytopenia (ITP) causes low platelet counts, variable bleeding symptoms, and reductions in health-related quality of life (HRQoL). Despite this, novel therapies for newly diagnosed ITP have not been introduced in over 30 years. Eltrombopag, a thrombopoietin receptor agonist (TPO-RA), was FDA approved for children with chronic ITP in 2015. The use of eltrombopag for adults with newly diagnosed ITP has been described in two small single-center trials (Tripathi et al, Int J Hematol, 2014; Gόmez-Almaguer et al, Blood, 2014), and pediatric hematologists do use TPO-RAs off-label in some cases of newly diagnosed ITP (Neunert et al, Pediatr Blood Cancer, 2016). TPO-RAs may be an efficacious and more durable first-line therapy for children with newly diagnosed ITP who require treatment. This abstract provides a 4-year interval update on the Pediatric ITP Newly diagnosed patients Eltrombopag vs Standard therapy (PINES) trial in progress. Study Design and Methods: The PINES trial, NCT03939637, is an investigator-initiated prospective, open label, randomized, multi-center trial sponsored by the ITP Consortium of North America (ICON) and funded by Novartis. The primary objective is to determine if the proportion of patients with a platelet response, defined as ≥3 of 4 platelet counts &amp;gt;50 x10 9/L during weeks 6-12 without rescue treatment, is significantly greater in patients with newly diagnosed ITP treated with eltrombopag compared to those treated with standard first-line therapy. Patients (n=162) from 30 ICON centers (Figure) are randomized 2:1, stratified by age and treatment status, to receive the experimental treatment, eltrombopag, or investigator's choice of 3 standard first-line therapies: prednisone, intravenous immune globulin or anti-D globulin at standardized doses. Eligible patients are ages 1 to &amp;lt;18 with primary ITP, within 3 months of diagnosis, with platelet count &amp;lt;30 x10 9/L who require pharmacologic treatment from the perspective of the treating clinician. Baseline treatment status is 1) upfront treatment, or patients within 10 days of ITP diagnosis with no prior treatment, and 2) treatment failure, or patients previously managed with observation or a first-line standard agent. Patients are ineligible if they can be observed without medication or have severe bleeding. A one-sided z-test, at alpha=0.025, will be used to compare the proportion of patients who have a platelet response between the two treatment arms. All randomized patients will be analyzed in the intention-to-treat analysis. Secondary objectives include treatment arm comparison of bleeding scores (WHO Bleeding Scale and Modified Buchanan Score), changes in HRQoL (measured by the Kids ITP Tool, Hockenberry Fatigue Scale, PROMIS, and Global Change Scale), and changes in percentage of CD4 +25 +Foxp3 + regulatory T (Treg) cells. Due to challenges related to recruitment and the logistics and safety of obtaining frequent assessments during the COVID-19 pandemic, the primary endpoint was re-defined in 2021 to what is considered a clinically equivalent definition of response, from ≥6 of 8 weekly to ≥3 of 4 biweekly platelet counts &amp;gt;50 x10 9/L during weeks 6-12. Baseline Characteristics: Since first site activation in 2019, 100 patients have been enrolled (Table). Subjects include 42 patients aged 1-&amp;lt;6 years, 34 patients aged 6-&amp;lt;12 years, and 24 patients aged 12-&amp;lt;18 years. Thirty-six patients received upfront treatment and 64 patients had treatment failure prior to enrollment. Median baseline platelet count at enrollment was 5 x10 9/L (range 1 - 28 x10 9/L). Median WHO Bleeding Scale at enrollment was 1 (range 0 - 3) and median modified Buchanan Overall Score was 3 (range 0 - 3). Baseline HRQoL surveys have been obtained for &amp;gt;80% of eligible subjects. Treg samples have been obtained for 95% of subjects, and 74% of subjects have consented to optional biology studies. Conclusion: Despite historical difficulty completing interventional trials in pediatric ITP and pandemic-related enrollment challenges, PINES trial enrollment is progressing successfully and will ultimately provide definitive data regarding the efficacy of eltrombopag in children with newly diagnosed ITP. There are no current data supporting the use of TPO-RAs for newly diagnosed ITP in children, or as monotherapy for newly diagnosed ITP in adults. Results from this trial therefore carry the potential to change management practices in ITP.

Quality of Life in Childhood Immune Thrombocytopenia: Revision of the Kids' ITP Tools (KIT)

Introduction New treatment approaches have emerged for pediatric ITP over the years, potentially impacting the health-related quality of life (HRQoL) of affected individuals. The Kids' ITP Tools (KIT) (Child self-report/Parent proxy-report and Parent impact-report) have gained international attention as valid tools for monitoring HRQoL in children with ITP and the impact on their parents. The questionnaires were recently updated to reflect changes in clinical management. However, it has also become common practice to evaluate the impact of new therapies using domain scales of QOL (i.e., sub-categories), which are not yet available for the KIT. Thus, the primary objective of this study was to establish domain scales for the KIT 2.0 that accurately quantify and identify specific aspects of HRQoL that are impacted in children with ITP and their parents. Methods The study was conducted in two sequential phases. Phase 1 involved ITP experts identifying key conceptual domains for the KIT questionnaires based on their clinical experiences. An online survey (“card sort survey”) was distributed, and experts sorted the current KIT 2.0 questions into domains, with domain headings suggested as well. Phase 2 involved a statistical approach (i.e., exploratory factor analysis (EFA)) to yield models with different number of domains. Data from children with ITP and their parents was utilized to develop the models, and the data was specifically from three previous international multicentre studies: ITP Consortium of North America (ICON1 study), UK Children's Hospital (UK ITP Paediatric Registry), and the Children's Hospital of Eastern Ontario (KIT international validation). Results In Phase 1, 24 experts completed the Child self-report card-sort survey, while 12 experts completed the Parent impact survey. There were two models that were derived for the Child Self-Report, with one having three domain scales and the other with four domain scales. The Parent Impact resulted in only one model that had three domain scales. In Phase 2, exploratory factor analysis (EFA) resulted in three models for each of the three questionnaires (Table 1), with the final models selected from the EFA and based on clinical interpretability. The four-domain model was selected for the Child Self-Report. The model had a higher Tucker Lewis Index (TLI) score and cumulative percentage of variance compared to the three-domain model. Though the cumulative percentage of variance was higher for the six-domain model, the model had two domains that each contained only two questions, which is not ideal for face validity. The final domain headings for the Child self-report were derived from the expert card sort survey: ITP Uncertainty; General symptoms; ITP challenges/disruptions; and Loss of control. The four-domain model was also selected for the Parent proxy-report on the basis of the same factors as the Child self-report. Likewise, the four-factor model had higher TLI score and relatively lower root mean square error of approximation (RMSEA) compared to the three-factor. The six-factor model had an ideal RMSEA, but contained one domain that had only two questions. The final domain headings are the same as the Child self-report as the context of the questions are the same. The four-domain model was selected for the Parent impact-report. Though both the four- and six-factor models contained two domains with only two questions each, the two-factor model was not ideal clinically as the questions within each of the two domains were not all similar. The headings were also derived from the expert card-sort: ITP Uncertainty; Treatment; Functional well-being; and Activities. Conclusion The revised KIT 2.0 aims to comprehensively summarize health-related quality of life in pediatric patients with ITP and their parents. The introduction of a domain structure derived from expert- and patient-data to the KIT will enable identification of specific aspects of QOL that are affected, which is imperative given the introduction of novel pharmaceutical agents in ITP treatment.

Efficacy and Safety Study of Switching from Hetrombopag or Eltrombopag to Avatrombopag in Childhood ITP

Background: Primary immune thrombocytopenia (ITP) in children is an acquired, immunologic, hemorrhagic disorder of childhood characterized by an isolated decrease in platelet count without a clear trigger. The main pathogenesis is an immune intolerance that mediates platelet immunodestruction and underproduction. The first-line treatment options for ITP are glucocorticoids and immunoglobulins, and TPO-RAs are the first choice for second-line treatment, including eltrombopag, hetrombopag, and avatrombopag and romiplostim. The 2019 International Consensus Report on the Investigation and Management of Primary Immune thrombocytopenia recommends that switching from one TPO-RA to another TPO-RA and sequential therapy in adult patients with multiple treatment failure have been shown to have positive effects on response and adverse events. However, in the treatment of childhood ITP, the experience of the conversion between TPO-RAs is insufficient. In this study, we retrospectively analyzed the treatment status of conversion of hetrombopag or eltrombopag to avatrombopag in children with ITP in our center, and explored the efficacy and safety of conversion therapy of avatrombopag. Methods: A total of 11 patients with primary ITP who switched from hetrombopag or eltrombopag to avatrombopag for any reason between May 2021 and May 2023 were included in this study. Patients were ≤15 years of age, had been treated with hetrombopag or eltrombopag for at least 4 weeks, and the interval between discontinuation of hetrombopag or eltrombopag and initiation of avatrombopag was no more than 1 month. The secondary endpoint of observation was 2 weeks after switching to avatrombopa, and the primary endpoint was 3 months after switching to avatrombopa. Observations included platelet reactions, dose of avatrombopag, tapering of other immunosuppressive agents, and treatment-related adverse events. Results: The median platelet count of patients was 30.1×10 9/L (8.4×10 9/L,89×10 9/L) before treatment with avatrombopag, 253×10 9/L (25×10 9/L,1179×10 9/L) after 2 weeks of avatrombopag（ P=0.003）, and after 3 months of avatrombopag the median platelet count was 343×10 9/L (53×10 9/L,803×10 9/L) （ P=0.008）. The platelet response rate was 90.9% after 2 weeks of treatment with avatrombopag, with a complete response rate of 63.6%, a partial response rate of 27.3%, and a no response rate of 9.1%; the platelet response rate was 100% after 3 months of treatment with avatrombopag, with a complete response rate of 88.9% and a partial response rate of 11.1%. The median onset of action was 9 (3,21) days. During the observation period, 8 of 11 patients were able to achieve avatrombopag dose reduction therapy with a median time to dose reduction of 13 days (4,86). Eight patients who were receiving concurrent immunosuppressive therapy prior to switching to avatrombopag, including six on prednisone and two on cyclosporine, were able to discontinue immunosuppressive therapy after switching to avatrombopag, with a median time to discontinuation of 18 days (12,24). The monitoring of liver and kidney functions, etc. during the observation period did not show any significant abnormality, and no thrombotic manifestations were found. Conclusion: The results of the pediatric data analysis in this study validate the potential value of switching between TPO-RAs: when one TPO-RA fails to provide sufficient efficacy, switching to another TPO-RA treatment may have a positive effect.

Prediction of the Clinical Course of Immune Thrombocytopenia in Children by Platelet Kinetics

Childhood immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by isolated thrombocytopenia. Prolonged ITP (persistent and chronic) leads to a reduced quality of life for children in many domains. To provide optimal support for children, with ITP, it is important to be able to predict those who will develop prolonged ITP. This study aimed to develop a mathematical model based on platelet recovery that allows the early prediction of prolonged ITP. In this retrospective study, we used platelet counts from the 6 months following the diagnosis of ITP to model the kinetics of change in platelet count using a pharmacokinetic–pharmacodynamic model. In a learning set (n = 103), platelet counts were satisfactorily described by our kinetic model. The Kheal parameter, which describes spontaneous platelet recovery, allowed a distinction between acute and prolonged ITP with an area under the curve (AUC) of 0.74. In a validation set (n = 58), spontaneous platelet recovery was robustly predicted using platelet counts from 15 (AUC = 0.76) or 30 (AUC = 0.82) days after ITP diagnosis. In our model, platelet recovery quantified using the kheal parameter allowed prediction of the clinical course of ITP. Future prospective studies are needed to improve the predictivity of this model, in particular, by combining it with the predictive scores previously reported in the literature.

Is Childhood Immune Thrombocytopenia Associated With Acquired Toxoplasmosis? An Unusual Case of Infection That Led to Acute ITP in a Greek Male Toddler and Implications for Guidelines.

Childhood immune thrombocytopenic purpura (ITP) is a heterogeneous immune-mediated process triggered by infections, vaccines, allergies and parasites. Currently, there is little evidence in the literature beyond case reports of an association with Toxoplasma gondii (T. gondii). The authors describe the unusual case of an earlier healthy 2.5-year-old Greek boy who developed acute ITP with a life-threatening platelet count a few days after a T. gondii infection. Evidence for the infection onset was found incidentally 3 months after the initial admission to the hospital and only after any other plausible cause of thrombocytopenia was excluded, according to diagnosis guidelines. The boy underwent 3 intravenous immunoglobulin treatments within a trimester, a period during which his alarming platelets count levels led to housebound activities. A quite slow recovery was only ignited after the third treatment, which was administered in conjunction with a mild antibiotic medication for the T. gondii infection. Full recovery was obtained 9 months after the initial admission, although the boy's potential scored high in clinical prediction models for developing transient ITP. There is a need for more research on ITPs with no obvious cause to investigate a causal association with toxoplasmosis. Currently, testing for diseases of greater rarity and of higher diagnostic cost than T. gondii is included in the ITP guidelines. Hence, routinely testing for toxoplasmosis when considering potential childhood ITP triggers and infection treatment complementary to treating the ITP might be the key to accelerating the healing process and improving the quality of life of otherwise confined children.

&lt;i&gt;Helicobacter pylori&lt;/i&gt; infection in children with immune thrombocytopenia

To detect the association between Helicobacter pylori (H. pylori) infection and immune thrombocytopenia in children and adolescents. Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. H. pylori is a widespread organism that is present in about 50% of the global population. There is an obvious relation between helicobacter pylori infection and chronic idiopathic thrombocytopenic purpura. A cross-sectional study was conducted in 95 patients with ITP who were recruited from the Hematology Unit, Department of Pediatrics, Menoufia University Hospital in the period from June 2021 to June 2022. The age of the patients ranged between 3.5 and 7.5 years. Fifty-five of them were males and 40 were females. The study was approved by the Ethical Committee of the Faculty of Medicine, Menoufia University. Out of the studied ITP children, 62 (65.3%) were positive for H. pylori antigen in stool, and 33 (34.7%) were negative. There was a significant difference between H. pylori-positive and H. pylori-negative patients regarding the grade of bleeding at presentation; 51 (82.3%) H. pylori-positive patients presented with grade 3 bleeding, 35 (56.5%) of them presented with skin and gum bleeding, 16 (25.8%) presented with skin bleeding and epistaxis. There was a statistically significant difference in the rate of recovery between H. pylorinegative patients (78.8%) and H. pylori-positive patients (22.6%). There was a significant rise in the platelet count in H. pylori-positive patients after the treatment of H. pylori. The prevalence of H. pylori infection in ITP pediatric patients was 65.3%. There was a significant rise in the platelet count in H. pylori-positive ITP children after the treatment of H. pylori.

Immune Thrombocytopenia in Children with Neurofibromatosis Type 1

Immune Thrombocytopenia in Children with Neurofibromatosis Type 1

Predictor Factors for Chronicity in Immune Thrombocytopenic Purpura in Children.

(1) Background: Immune thrombocytopenia (ITP) is an acute autoimmune blood disorder that is the main cause of thrombocytopenia in children. It is characterized by a decrease in platelets below 100 × 109/L, and limited evolution with severe complications such as intracranial hemorrhage. The chronic form is defined by the persistence of thrombocytopenia more than 12 months after diagnosis. (2) Methods: We performed a retrospective study over a period of 10 years (1 January 2011-31 December 2020) at the Emergency Clinical Hospital for Children "Sf. Maria", Iasi. The aim of the study was to describe the clinical characteristics and to determine the prognostic factors in immune thrombocytopenia in children. (3) Results: In this study we included 271 children with ITP, comprising 123 females (45.4%) and 148 males (54.6%). The remission rate was higher in males, being 68.9% compared to 56.1% in females. Children with ITP under 9 years of age had a higher remission rate. Children with a platelet count > 10 × 109/L at diagnosis had a higher likelihood-of-remission rate compared to patients who presented initial platelet count below this value. (4) Conclusions: The risk factors highly suggestive for chronicity are: age at diagnosis, female sex, and the number of platelets at the onset of the disease.

Thrombopoietin receptor agonists in pharmacotherapy of pediatric immune thrombocytopenia

Introduction: Thrombopoietin receptor agonists are commonly second-line drugs in immune thrombocytopenia (ITP) pharmacotherapy in children and prescribed for chronic ITP refractory to first-line therapy.&#x0D; Standard ITP pharmacotherapy in children: includes prescribing glucocorticoids or intravenous immunoglobulins.&#x0D; Thrombopoietin receptor agonists: Currently Romiplostim and Eltrombopag are used in the Russian Federation pediatrics. Their pharmacodynamic features in comparison with other drugs used in ITP are presented in the paper. Increased thrombocytopoiesis is the dominant, but not the only component of Romiplostim and Eltrombopag mechanism of action. It is relevant to study their effect on immune tolerance in ITP, which may be associated with a persistent platelet response in some patients after drug discontinuation.&#x0D; Conclusion: The issue of thrombopoietin receptor agonist efficacy and safety as well as the mode of their use in ITP children treatment continues to be studied. The high cost of drugs continues to be a limiting factor to their earlier prescription. Generic drugs – Romiplostim and Eltrombopag partly solve the problem, promote their earlier prescription in ITP, but require additional study of their bioequivalence and therapeutic equivalence in comparison with the original drugs.&#x0D; Graphical Abstract&#x0D; &#x0D;

Intravenous immunoglobulins ameliorate thrombin-related platelet functions in childhood immune thrombocytopenia.

Childhood immune thrombocytopenia (ITP) is an acquired haematological disorder characterized by low platelet counts, with a disease course which is usually benign and self-limiting within 3-12 months. An estimated 28%, however, continue to develop chronic ITP and may experience bleeding symptoms and an impaired quality of life. Treatment options in case of severe bleedings include corticosteroids, anti-D or intravenous immunoglobulins (IVIg). The general working mechanism of IVIg remains unresolved and a matter of debate. Schmugge et al now identify that IVIg may have the ability to improve thrombin-induced platelet activation and enhance thrombin generation in a prospective study of 23 children with primary ITP, demonstrating that besides increasing platelet counts IVIg can be efficacious on the level of thrombin-induced platelet activation and coagulation support. Commentary on: Schmugge et al. IVIg treatment increases thrombin activation of platelets and thrombin generation in paediatric patients with immune thrombocytopenia. Br J Haematol 2023;201:1209-1219.

Clinical Characteristics Analysis of Immune Thrombocytopenia in Children

To analyze the clinical characteristics of immune thrombocytopenia (ITP) in children and explore the risk factors of chronic immune thrombocytopenia (CITP) . The clinical data of children newly diagnosed with ITP in the Department of Pediatrics of the First Affiliated Hospital of Wannan Medical College from January 2015 to December 2020 were retrospectively analyzed, information on age of onset, sex, blood type, platelet count at the time of initial diagnosis, mean platelet volume, lymphocyte count, platelet-related antibodies, time to normalization of platelets, and the presence of prodromal infections. The 180 cases that met the requirements were selected according to the inclusion and exclusion criteria, with at least 1 year of outpatient and telephone follow-up. The risk factors affecting the prognosis of the children were derived by univariate and muitivariate binary logistic regression analysis, and the predictive value of the risk factors was evaluated by the receiver operating characteristic curve. A total of 180 children with ITP were collected in this study, including 36 cases of chronic ITP (20%) and 144 cases of nonchronic ITP (80%). The results of univariate analysis showed that the age≥3 years, lymphocyte count≥（3.98±2.26）×109/L, and time to normalization of platelets≥（4.38±1.79）d at the time of initial diagnosis were adverse prognostic factors of CITP. The results of muitivariate analysis showed that the children with ITP aged ≥3 years (OR=3.792, 95%CI: 1.427-10.075, P=0.008), children with longer time to normalization of platelets (OR=1.295, 95%CI: 1.055-1.591, P=0.014) were more likely to develop CITP. The results of the receiver operating characteristic curve showed that the area under the curve for age prediction of CITP was 0.715, with a sensitivity of 80.6% and specificity of 61.1%; when the platelet return to normal was 4.5 days. The maximum area under the ROC curve was 0.708, with a sensitivity of 75% and specificity of 59.9%, both of which had good values for predicting CITP. Age≥3 years and longer time to normalization of platelets（≥4.5 days） are risk factors for CITP and have good value in predicting CITP, while gender, blood group, platelet count at initial diagnosis, mean platelet volume, plateletrelated antibodies, and presence of antecedent infection are not significantly correlated with CITP.

Relationship between coronavirus disease 2019 vaccination and the risk of immune thrombocytopenia

To study the relationship between coronavirus disease 2019 (COVID-19) vaccination and the risk of immune thrombocytopenia (ITP). A retrospective analysis was conducted on children aged 3-17 years with newly diagnosed ITP who were hospitalized in Children's Hospital Affiliated to Zhengzhou University from November 2021 to December 2022. Clinical data and COVID-19 vaccination status were compared among three groups: ITP patients vaccinated within 12 weeks before onset, vaccinated more than 12 weeks before onset, and unvaccinated. Changes in serum immunoglobulin and complement levels were analyzed among five groups: ITP patients vaccinated <4 weeks before onset, 4-<8 weeks before onset, 8-<12 weeks before onset, ≥12 weeks before onset, and unvaccinated. A case-control design was used to estimate the risk of ITP: 387 children aged 3-17 years with fractures hospitalized during the same period in the emergency department of the hospital were selected as the control group, and the exposure to COVID-19 vaccination within 12, 8, and 4 weeks before onset in ITP children was compared to estimate the risk of ITP. Among 129 ITP children, there were no statistically significant differences in age, gender, rate of preceding infections, absolute platelet count at initial diagnosis, absolute lymphocyte count at initial diagnosis, bleeding score, positive anti-nuclear antibody rate, absolute platelet count after 4 days of treatment, recurrence rate, and proportion of patients with disease duration ≥3 months among the three groups vaccinated within 12 weeks before onset, vaccinated more than 12 weeks before onset, and unvaccinated (P>0.05). There was a statistically significant difference in serum immunoglobulin G, immunoglobulin A, and complement component 3 levels among the groups vaccinated <4 weeks, 4-<8 weeks, 8-<12 weeks, and ≥12 weeks before onset, and unvaccinated (P<0.05). The risk estimation results showed that COVID-19 vaccination within 12 weeks, 8 weeks, and 4 weeks before onset did not increase the risk of ITP (P>0.05). COVID-19 vaccination does not increase the risk of ITP.