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Background: There is limited information on the natural course of chronic ITP in children. We aimed to evaluate the clinical and demographic characteristics of children with chronic ITP in the era before the availability of eltrombopag. Methods: A total of 86 children with chronic ITP between 1978–2014 were included. Demographic findings, laboratory results, clinical signs, bleeding scores, response time and time of complete remission were recorded. Results: The male/female ratio was 1.09, and median follow-up time was 3 years (range: 1.5–17 years). The median age at diagnosis of chronic ITP was 7 years (range: 2–17), and the median initial platelet count was 10 × 109/L (range: 1–66 × 109/L). Petechiae/ecchymoses were the most common clinical sign (86%) and followed by mucosal bleeding (39.5%). Severe bleeding was seen in 5% of the patients. None of them had intracranial hemorrhage. Twenty patients underwent splenectomy, and the rate of complete remission was 70%. Spontaneous complete remission was seen in 29% of the patients, and the median time to spontaneous complete remission was 3 years. Conclusions: Our study showed that almost one-third of patients with chronic ITP experienced spontaneous complete remission in an average of 3 years, and splenectomy provided satisfactory results in severe cases. This study demonstrates the natural history of chronic ITP in childhood before the era of eltrombopag. [ABSTRACT FROM AUTHOR]

Background: Primary immune thrombocytopenia (ITP) represents the commonest cause of isolated thrombocytopenia among children & adolescents; that's characterized by variable presentations and varied outcomes of disease differentiated into; acute, persistent, or chronic depending upon illness duration; with efforts made to increase knowledge about possible outcome predictors. Aim: we aimed to study disease characteristics & outcome predictors among 50 enrolled patients. Methods: This retrospective cohort study included collection of; demographic data, bleeding phenotype, Buchanan bleeding score onset of symptoms prior to diagnosis, proceeding viral infection or vaccination, initial platelet count & bone marrow finding, received treatment as well as; response to treatment among 50 patients already diagnosed as primary ITP child and adolescent which followed up since 2012 till 2020 in pediatric hematology clinic, Ain Shams University. Patients were further subdivided into acute, persistent & chronic ITP groups. Results: Among included cohort; 38 (76.0%) were males of median (IQR) age of 5.25 (2.5-8.5) years. Chronic ITP represented the most prevalent outcome in the cohort 58.0%(n=29), with acute ITP 32.0%(n=16) & persistent ITP 10.0% (n=5). Among the chronic ITP group in comparison to other groups; female was more than third the patients 34.5% (n=10), 72.4%(n=21) reported >2weeks disease related symptoms with no seasonal peaks of diagnosis, 10%(n=1) presented initially with menorrhagia, Yet no statistical differences between groups regarding associated autoimmune symptoms, bleeding score, nor initial platelet count (p= 0.91, p=0.078, p=0.955) respectively. All chronic ITP groups required steroids in initial treatment with significant difference in response to treatment & recurrence of the disease (p=0.00) as none showed complete remission and all patients experienced disease recurrence. Conclusion: Different presentation of primary ITP. e.g. gender, bleeding symptoms, treatment among children can potentially serve as clinical predictors of outcome. [ABSTRACT FROM AUTHOR]

Background: There is limited information on the natural course of chronic ITP in children. We aimed to evaluate the clinical and demographic characteristics of children with chronic ITP in the era before the availability of eltrombopag. Methods: A total of 86 children with chronic ITP between 1978–2014 were included. Demographic findings, laboratory results, clinical signs, bleeding scores, response time and time of complete remission were recorded. Results: The male/female ratio was 1.09, and median follow-up time was 3 years (range: 1.5–17 years). The median age at diagnosis of chronic ITP was 7 years (range: 2–17), and the median initial platelet count was 10 × 109/L (range: 1–66 × 109/L). Petechiae/ecchymoses were the most common clinical sign (86%) and followed by mucosal bleeding (39.5%). Severe bleeding was seen in 5% of the patients. None of them had intracranial hemorrhage. Twenty patients underwent splenectomy, and the rate of complete remission was 70%. Spontaneous complete remission was seen in 29% of the patients, and the median time to spontaneous complete remission was 3 years. Conclusions: Our study showed that almost one-third of patients with chronic ITP experienced spontaneous complete remission in an average of 3 years, and splenectomy provided satisfactory results in severe cases. This study demonstrates the natural history of chronic ITP in childhood before the era of eltrombopag.

Chronic immune thrombocytopenic purpura (ITP) is one of the most frequent immune hematological disorders in which development the leading part is played by the antibodies directed against a narrow spectrum of platelet antigens. Though death rate at chronic ITP is insignificant, no more than 1%; disease strongly reduces patients quality of a life, and frequently requires difficult and expensive treatment. Antiplatelets antibodies mediating ITP, are directed against glycoprotein GP IIb/IIIa and, less often, GP Ib/IX. At ITP can be registered both raised bone marrow platelet production and accelerated peripheral blood platelet clearance, and strongly decreased production and normal platelet life-span. Antibodies to platelet membrane glycoproteins directly disturb platelet production in bone marrow. Standard drug interventions at chronic ITP - glucocorticoids in various doses, high doses intravenous immunoglobulin, anti-D immunoglobulin, rituximab - rare lead to stable increase platelet number while in 2/3 patients splenectomy is effective. The new therapy approach in chronic ITP is stimulation of platelet production in bone marrow. Recombinant fusion protein Romiplostim stimulates trombopoietin receptor and it is effective at long-term therapy in 87% patients with chronic ITP irrespective of previous splenectomy. TPO antibodies development with romiplostim therapy was not revealed.

Background : : This study aimed to identify chronicity predictors of pediatric primary immune thrombocytopenia (ITP). Methods : : This study retrospectively reviewed the medical records of patients with primary pediatric ITP admitted to a tertiary medical center between 2010 and 2021. Forty-five patients with a platelet count

Immune thrombocytopenia in children is defined by a decrease in platelet counts < 100 x 109/L. The incidence of the disease varies from 1.6-6 per 100,000 children. Oral hemorrhagic manifestations (petechiae, epistaxis, gingivorrhagia, soft and hard palate hemorrhagic blisters) may be the first manifestations of the disease. Age over 1 year at diagnosis and the sudden onset of the symptom are the most important predictors of chronic disease. Oral hemorrhagic manifestations in ITP (immune thrombocytopenic purpura) in children are a warning sign in the evolution of the disease and a therapeutic challenge. Corticosteroid therapy and IV immunoglobulin, are the first therapeutic line to follow. A multidisciplinary approach is a necessity for the proper management of the child with ITP.

Background: Immune thrombocytopenia (ITP) is a benign childhood disease. The aim of this study was to assess Health Related Quality of Life (HRQoL) among chronic ITP children in Vietnam. Methods: A case - control study was conducted from January 2020 to April 2021. Case group consisted of 56 children with chronic ITP aged from 2 to 18 years and their parents selected in the Department of Nephrology-Hematology – Endocrinology, Haiphong Children's Hospital, Hai Phong city. Controls included 170 healthy children matched with the patients on sex, and age recruited from schools in the same city. The validated Vietnamese version of the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scale was used to assess QoL of the participants. Results: The mean HRQoL physical, emotional, social, school functioning domains and total scores of the chronic ITP patients were significantly lower compared with that of the controls (p

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83. Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources.

There are no definitive guidelines for management of chronic or refractory immune thrombocytopenia (ITP) in children. Dapsone is an inexpensive and efficacious, yet neglected, therapeutic option for treatment of chronic ITP. We evaluated the efficacy and safety of dapsone in the management of chronic ITP in children. Children with chronic ITP < 14 years with minimum grade 2 bleeds refractory to either splenectomy/rituximab/eltrombopag; who were offered dapsone therapy were retrospectively analyzed. Dapsone intolerance and G6PD deficiency were excluded. Dapsone was started at a dose of 1–2 mg/kg/day. Response to dapsone as per international working group definitions, time to response along with side-effects were noted. Forty-four children enrolled; 29 analyzed. Nineteen were refractory to rituximab, 8 to splenectomy and 6 to eltrombopag. Median age was 9.8 years (3–14) with 16/29 males. Median dapsone dose was 1.59 mg/kg/day (range 1–2.1). Overall response was seen in 21/29 (72%): Complete Response in 7/29 (24%), Partial Response in 14/29 (48%). All responses were sustained for minimum 3 months. Median duration to response was 2.9 months (2–6.6). Median follow up was 28 months (6–73) and relapse rate-21%. Major side effects noted: Methemoglobinemia-01, skin ulceration-02. In three cases dapsone could be tapered and stopped without relapse. Dapsone is an economical and efficacious agent with good safety profile in childhood chronic/refractory ITP. [ABSTRACT FROM AUTHOR]

Inherited macrothrombocytopenia is increasingly being recognized as a relatively common condition. This descriptive review aims at focusing on the different areas of advancement that have taken place with this condition with particular reference to India. A pubmed search of articles between January 1990 and October 2017 with the key words-macrothrombocytopenia, asymptomatic macrothrombocytopenia, macrothrombocytopenia India, syndromic macrothrombocytopenia, molecular pathology, megakaryopoiesis and platelet formation were searched. The shortlisted articles were then read. Review articles provided additional references and the articles thus obtained were also read. Special interest and research conducted by the authors provided further sources of information. A total of 487 articles were found of which 68 articles were related to our subject of review. Review articles were read and additional articles from the reference quoted. Forty-four percent of nonsyndromic Inherited macrothrombocytopenia showed mutations of MYH9, GP1BB, GP1Ba, GPIX, ABCG5 and 8, ACTN, FLI, TUBB and RUNX1 frequently in heterozygous state. All types of inheritance pattern namely autosomal dominant, recessive and sex linked patterns have been described. Syndromic causes of this phenomenon are well known and have been described. Many asymptomatic patients do have mild or moderate bleeding history. Clinical algorithms to differentiate chronic ITP associated macrothrombocytopenia from inherited variety have been explored. Inherited macrothrombocytopenia is an emerging area of interest in platelet biology with its implication in diagnosis, prognosis, genetic counseling, management and in transfusion medicine. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is an epigenetic process that refers to chromatin-based mechanisms in the regulation of gene expression without DNA alternation. It is mediated by DNA methyltransferases (DNMTs). The DNA methyltransferase 3B (DNMT3B) gene contains a C-to-T single nucleotide polymorphism (SNP; rs2424913) in the Promotor region, 149 base pairs from the transcription start site, which is reported to significantly increase the Promotor activity. Objective: To investigate the prevalance of rs2424913 single nucleotide polymorphism located in the DNMT3B gene Promotor. Methods: In the present study, we investigated the prevalence of rs2424913 single nucleotide polymorphism located in DNMT3B gene Promotor by restriction fragment length polymorphism (PCR-RFLP) in Egyptian pediatric chronic immune thrombocytopenia (ITP) patients and controls. Results: The homozygous genotype (TT) was significantly higher in our patient and conferred almost 3-fold increased risk of chronic ITP when compared to controls. Conclusion: The present study shows that DNMT3B rs2424913 promotor polymorphism represents a genetic risk factor that may play an important role in understanding the pathogenesis of chronic ITP. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) results in part from the presence of platelet antibodies, which can be demonstrated by the Monoclonal Antibody-Specific Immobilization of Platelet Antigens (MAIPA) assay. The aim of our study was to correlate the presence of antiplatelet autoantibodies and the natural history of ITP. We performed a retrospective, single-center study of 108 adults with newly diagnosed ITP who had indirect MAIPA assay performed at disease onset. Chronic ITP was defined by the presence of thrombocytopenia after 1 year. Bleeding diathesis was evaluated with a bleeding score. At baseline, patients with a positive indirect MAIPA have a greater bleeding score than patients with negative MAIPA assay [median (interquartile) = 8 (6-12) vs 2 (0-6), p = 0.002]. Patients with a positive indirect MAIPA also had a higher rate of chronic ITP (92.9 vs 68.7 %, p = 0.06). In multivariate analysis, a positive indirect MAIPA result and a platelet count at onset ≥10 × 10/L remained independently associated with chronic ITP [adjusted OR (aOR) = 8.01; 95 % confidence interval (CI), 0.98-66.6; p = 0.05 and aOR = 3.09; 95 % CI, 1.18-8.10; p = 0.02, respectively]. Furthermore, when we analyzed together the results of direct ( n = 41) and indirect MAIPA, the same results were observed. Thus, indirect MAIPA positivity at disease onset is associated with more severe hemorrhage and predicts a chronic course in adult ITP patients. MAIPA assay could be useful in the management of ITP patients when it is performed at diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To assess the validity and reliability of the fatigue subscale of the Functional Assessment of Chronic Illness Therapy (FACIT-F), a 6-item subset from the thrombocytopenia subscale of the Functional Assessment of Cancer Therapy (FACT-Th6) and the Short Form-36 Version 2 (SF-36v2) in 2 clinical trials of the thrombopoietin receptor agonist eltrombopag in chronic immune thrombocytopenia (ITP) patients. Methods: In the 6-month, RAndomized placebo-controlled ITP Study with Eltrombopag (RAISE; n = 197), the FACIT-F, FACT-Th6, and SF-36v2 were administered at baseline, day 43, weeks 14 and 26, or early withdrawal. In the ongoing open-label extension study, Eltrombopag EXTENDed Dosing Study (EXTEND; n = 154), measures were administered at baseline, at the beginning of each stage, and at permanent discontinuation of study medication. Results: FACIT-F, FACT-Th6, and SF-36v2 demonstrated acceptable internal consistency reliability (i.e., all Cronbach's alphas >0.70) and test-retest reliability (all intraclass correlation coefficients >0.70). Construct validity was supported by moderate (0.35 < r < 0.50) to strong ( r > 0.50) inter-measure correlations for baseline and change scores. A small to medium magnitude of effect was captured by the FACIT-F and FACT-Th6 among patients who experienced sustained platelet responses. Conclusions: Results provide support for the validity, reliability, and responsiveness of the FACIT-F, FACT-Th6, and SF-36v2 in chronic ITP patients. [ABSTRACT FROM AUTHOR]

Romiplostim stimulates thrombopoietin receptor to increase platelet production of megakaryocytes in idiopathic thrombocytopenic purpura (ITP). This study aimed to evaluate the safety and efficacy of romiplostim in children with chronic ITP. Eighteen patients with chronic ITP, either none responsive or failed to maintain response on two or more therapeutic modalities, were enrolled. Patients were randomized (2:1) to receive romiplostim or placebo for 12 weeks, initiated at 1 μg/kg/week, escalated to 5 μg/kg/week, and then tapered. Median patients' age was 8.5 years, and the median baseline platelet count (PC) was 10.5 × 10(9)/L. The median weekly dose of romiplostim was 2 μg/kg. Fifty percent of patients in both romiplostim and placebo arms had at least one adverse event (AE); none was serious. Ten patients on romiplostim (83.3%) maintained the efficacy endpoint (PC > 50,000). Romiplostim was well-tolerated and efficient in treating the children with chronic refractory ITP with no unexpected AEs. [ABSTRACT FROM AUTHOR]

Chronic ITP (immune thrombocytopenic purpura; now defined as duration of more than 12 months) is not always associated with significant bleeding problems so that most children and adults can be managed expectantly with no medication unless surgery, accidents or other pathology mandate it. A cut-off platelet count of 30 x 10(9)/l divides a group with no increased mortality from those whose risk is greater and in whom medication is usually appropriate. There is increasing recognition of long-term morbidity and mortality associated with immune suppression induced by medication and more recently new concerns have arisen about the long-term vascular complications of splenectomy. A more conservative approach to medication is warranted in many patients with chronic ITP. [ABSTRACT FROM AUTHOR]

With regards to research animal models related to immune thrombocytopenia (ITP), there is an extensive literature of over 300 publications published since 1959. It appears that many of these models either confirm what has been found in human ITP or, in some instances, are the first to describe a phenomenon related to ITP that is still of relevance today in human medicine. These models will undoubtedly play a significant role in the future research of human ITP particularly related to understanding of the pathogenesis of the disorder and the development of novel therapeutics. This review will highlight some of the major animal models utilized for ITP research and will present a somewhat historical aspect of the subject. [ABSTRACT FROM AUTHOR]

To evaluate the rituximab treatment in children with chronic immune thrombocytopenic purpura This study included ten children with chronic immune thrombocytopenic purpura, which were nonresponsive to Steroid (S), IVIG and anti-D treatments. Rituximab was given with a dosage of 375 mg/m2 weekly for 4–6 weeks. Initial platelet count was less than 30×109/L and responses were assessed in follow-up. The patients’ groups were categorized as complete remission (CR);a platelet count ≥150×109/L,partial remission (PR);a platelet count ranging from 50×109/L to 150×109/L, minimal remission (MR); a platelet count ranging from 30×109/L to 50×109/L and no response (NR); a platelet count less than 30×109/L. Of our patients, four female and six male, their ages ranged from 39 mth to 13 yr and the mean age was 83.4±44.58 mth. None of the patients was splenectomized. The follow-up period after rituximab treatment ranged between 12 to 42 mth and the mean follow-up period was 25.10±13.03 months. While on this treatment, we had a CR in two patients, a PR in one, a MR in three, but no response in four. The patients in CR/PR are still being followed as in remission and they have 40 mth of mean follow-up period. The three patients in MR had a decrease in values of platelets earliest in one mth and the latest in four mth. Adverse effects of rituximab, such as itching and scraps that were not clinically significant were observed in three patients during rituximab infusion. There were no increase in infections after rituximab in any patient. CR was found in 20% of our patients, PR in 10% and MR in 30% with rituximab. On this treatment, while some series had good outcomes with this treatment (72%–100%, remission ratios), but many series, such as ours, had a poor response rate contrast to many reported case series in the literature. This condition may be associated with the age of our most patients who were young at the time of commenced rituximab. However, we believe that more studies are required to elucidate the reasons for different results in different case series reported in literature. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100 × 109/l, partial remission (PR) if platelets were >50 × 109/l, minimal response (MR) if the platelet count was >30 × 109/l and <50 × 109/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5 × 109/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events. [ABSTRACT FROM AUTHOR]

Background: Occult hemorrhage can occur in any internal organ in ITP patients. Four sites of occult hemorrhage deserve special attention including microscopic hematuria, fecal occult blood, retinal hemorrhage, and silent intracranial hemorrhage. Aim: The aim of this study was to investigate for the frequency of subclinical bleeding in Egyptian children with ITP and its relation to different clinical and laboratory parameters of the disease. Methods: This cross-sectional study included 40 ITP patients recruited from the Pediatric Hematology& Oncology unit, Children Hospital, Ain Shams University. Occult blood in stools and urine analysis, fundus examination, and non-contrast brain MRI, for brain microbleed, were done. Results: The total number of patients with occult bleeds was eleven. Two patients had occult blood in stool, five had microscopic hematuria, one had retinal bleeds and three patients had brain microbleeds. Nine patients with occult bleeding were chronic, one persistent and one acute ITP patients. Their mean age was 10.23 6 4.18 and their mean initial bleeding score was 2.55 6 0.82.There were no significant differences between patients with occult bleeding and those without as regards the platelet counts & hemoglobin level, as well as the mean platelet counts & mean hemoglobin level over the disease duration. Conclusion: Our results suggest that subclinical bleeding is a potential risk in children with ITP, more commonly chronic ITP patients. We could not demonstrate a significant relation of occult bleeding to the laboratory findings; nevertheless, the significance of the routine assessment of occult bleeding in ITP and the identification of high-risk patients require additional studies. [ABSTRACT FROM AUTHOR]

Repeated courses of HD IVIg are reported to induce stable remission in a significant proportion of adults with chronic refractory ITP. We have treated 14 such patients obtaining a remission rate quite comparable to the 5-10% of spontaneous remission. [ABSTRACT FROM AUTHOR]