Current therapeutic practices in children with immune thrombocytopenia — Polish nationwide survey results

Immune Thrombocytopenia during Childhood: New Approaches to Classification and Management

Objective To discuss DNA methylation's effect on pathogenesis of pediatric immune thrombocytopenia (ITP)through detecting the expression level of DNA methyltransferases (DNMTs)mRNA in peripheral blood lymphocytes of children with ITP. Methods Two mL peripheral blood was collected from each of 25 children with persistent and chronic ITP and 20 healthy children(the healthy control group)by using aseptic method in the pediatric ward of the First Affiliated Hospital of Xinxiang Medical University from January 2014 to January 2015.First ethylenediamine tetraacetic acid (EDTA) was used as the anticoagulant.Then separate the mononuclear cells, extract RNA and detect expression levels of DNMT1, DNMT3A and DNMT3B mRNA using reverse transcription-polymerase chain reaction (RT-PCR) method. Results (1)The blood platelet(PLT) of children with persistent and chronic ITP was (36.2±19.6)×109/L, which was obviously lower than the healthy control group(168.8±46.8)×109/L(t=-11.85, P=0.000). (2)The DNMT1 mRNA expression level of children with persistent and chronic ITP was 0.17±0.05, which was obviously lower than the healthy control group (0.27±0.10) (t=-3.912, P=0.001). The DNMT3A mRNA expression level of children with persistent and chronic ITP was 0.20±0.10, which was obviously lower than the healthy control group (0.32±0.11) (t=-3.779, P=0.000). The DNMT3B mRNA expression level of children with persistent and chronic ITP was 0.16±0.11, which was obviously lower than the healthy control group (0.31±0.11) (t=-4.641, P=0.000). (3) There was positive correlation between the expression of DNMT1 and DNMT3B mRNA(r=0.433, P=0.031). There was positive correlation between the expression of DNMT3A and DNMT3B mRNA(r=0.721, P=0.000). Conclusions (1) Children with persistent and chronic ITP have lower expression levels of DNMT1, DNMT3A, DNMT3B mRNA, which indicates that DNA methylation contributes to the pathogenesis of pediatric persistent and chronic ITP.(2) DNMTs have synergistic effect on DNA methylation of pediatric persistent and chronic ITP. Key words: Child; Immune thrombocytopenia, persistent, chronic; DNA methyltransferase

Primary immune thrombocytopenia: understanding pathogenesis is the key to better treatments.

Intravenous Efgartigimod for the Treatment of Primary Immune Thrombocytopenia in Adults: A Planned, Phase 3, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Arm Study with Open-Label Period (ADVANCE NEXT)

Genes Influencing the Development and Severity of Chronic ITP Identified through Whole Exome Sequencing

Thrombopoietin Analogs In ITP Patients Daily Practice: Treatment Profile, Efficacy and Safety

Real World Romiplostim Dosing and Response in Pediatric Immune Thrombocytopenia

FCGR3A V/F 158 Polymorphism Is Not Associated with Response to Rituximab in adult's Immune Thrombocytopenia

Eltrombopag for Immune Thrombocytopenia Adult Patients in the Real-Life Practice in France. Interim Results of the Elextra Study

Avatrombopag for the treatment of children and adolescents with immune thrombocytopenia (AVA-PED-301): a multicentre, randomised, double-blind, placebo-controlled, phase 3b study.

Validation of Differentially Expressed Micrornas in Primary Immune Thrombocytopenia Suggests Mir-199a-5p Is a Potential Diagnostic Biomarker

Background The long-term outcome of primary immune thrombocytopenia (ITP) is unpredictable. Chronic ITP is common in adults, requiring second-line treatments with increased morbidity and mortality. Our study aimed to identify predictive factors of chronicity at the time of diagnosis in primary adult ITP. Research design and methods This retrospective multicenter study included adult patients newly diagnosed with primary ITP. Patients with a normal platelet count and no ongoing medication twelve months after disease onset were categorized in the complete remission ITP group, otherwise in the chronic ITP group. Results 219 patients were included, 110 in the complete remission ITP group and 109 in the chronic ITP group. In multivariate analysis, predictive factors of progression to chronicity included the absence of an infectious event preceding ITP onset (p = 0.048), the absence of bleeding manifestations (p = 0.002) and a platelet count >10 x 109/L at disease onset (p = 0.02). A poor response to initial corticosteroid treatment was also associated with chronicity, including corticosteroid dependence (p<0.001) and corticosteroid resistance (p = 0.001). Conclusions In this retrospective French cohort, predictors of chronicity in newly diagnosed primary adult ITP included the absence of preceding infectious event, platelet >10 x 109/L and absence of bleeding manifestations at onset.

To examine the expression of serum thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) in children with immune thrombocytopenia (ITP). A total of 120 children with ITP who were admitted from October 2019 to October 2021 were enrolled as the ITP group. A total of 60 children without ITP were enrolled as the non-ITP group. According to the clinical classification of ITP, the children in the ITP group were further divided into a newly diagnosed ITP group, a persistent ITP group, and a chronic ITP group. The clinical data were compared between the ITP group and the non-ITP group and between the children with different clinical classifications of ITP. The expression levels of serum TGAb and TPOAb in children with ITP were measured and their association with the clinical classification of ITP was analyzed. Compared with the non-ITP group, the ITP group had significantly lower levels of CD3+, CD4+, and platelet count (PLT) and significantly higher levels of CD8+, TGAb, and TPOAb (P<0.05). The children with chronic ITP had significantly lower levels of CD3+, CD4+, and PLT and significantly higher levels of CD8+, TGAb, and TPOAb than those with newly diagnosed ITP or persistent ITP (P<0.05). The logistic regression analysis showed that CD3+, CD4+, CD8+, TGAb, and TPOAb were the influencing factors for chronic ITP (P<0.05). A decision curve was plotted, and the results showed that TGAb combined with TPOAb within the high-risk threshold range of 0.0-1.0 had a net benefit rate of >0 in evaluating the clinical classification of ITP in children. TGAb and TPOAb are abnormally expressed in children with ITP and are associated with the clinical classification of ITP in children.

Two-Year Safety and Efficacy Outcomes with Fostamatinib in Adult Patients with Immune Thrombocytopenia (ITP): Open-Label Extension to Phase 3 Trial Program

Thrombopoietin (TPO) is the critical regulator of platelet production. However, the role of TPO in pediatric patients with thrombocytopenic disorders has not been fully elucidated. In the present study, we attempted to investigate serum TPO levels in patients with acquired aplastic anemia (aAA) and immune thrombocytopenia (ITP). We analyzed the endogenous plasma concentration of TPO and platelet count at the time of TPO measurement in 166 patients with aAA and 280 patients with ITP retrospectively. We further observed a correlation between platelet counts and TPO. Serum TPO levels were significantly higher in aAA compared with ITP (1142 vs. 77.99pg/mL, P <0.001). In patients with aAA, an elevation for TPO levels in very severe AA (VSAA) was seen when compared with non-severe AA (NSAA) (1360 vs. 984.4pg/mL, P <0.05). In contrast, the circulating TPO levels with chronic ITP (CITP) showed a decrease than newly diagnosed ITP (NITP) and persistent ITP (PITP) (62.28 vs. 81.56pg/mL, P <0.01, 62.28 vs. 87.82pg/mL, P <0.05, respectively). There was a negative correlation between platelet counts and TPO levels in aAA (r s =-0.3325, P <0.001) as well as ITP (r s =-0.2570, P <0.001). Especially, TPO levels were inversely correlated with platelet counts in NSAA (r s =-0.3672, P <0.001) and NITP (r s =-0.3316, P <0.001). After grouping by age or sex, there were no statistical differences in aAA or ITP. Serum TPO levels were markedly elevated in pediatric patients with aAA compared with ITP. It was higher in VSAA and lower in CITP, suggesting that serum TPO level could play a role in classifying disease severity or clinical course in aAA and ITP.