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Background: Platelet glycoprotein VI (GPVI) receptor is essential for platelet adhesion and aggregation. Eltrombopag is as an effective treatment for chronic immune thrombocytopenia (ITP); yet, its effect on platelet function is not fully characterized., Aim: This prospective study investigated the effect of eltrombopag therapy on platelet function through assessment of GPVI receptor expression and soluble GPVI levels among pediatric patients with persistent or chronic ITP., Methods: Thirty-six children and adolescents with persistent or chronic ITP were divided equally into two groups either to receive eltrombopag therapy or the standard of care. All patients were followed-up for 12 months with assessment of bleeding score and complete blood count (CBC). Evaluation of GPVI expression using flow cytometry and measurement of its soluble form by ELISA was done at baseline and at 6 months., Results: ITP patients on eltrombopag had significantly lower bleeding score after 6 months of therapy while the quality of life has significantly improved. Platelet count was significantly increased throughout the study. GPVI expression by flow cytometry and soluble GPVI levels were significantly increased after eltrombopag therapy. After 12 months, ITP patients on eltrombopag were able to maintain a good quality of life and low bleeding score., Conclusion: Our data suggest that eltrombopag, through its effect on the GPVI receptor expression and its soluble form, might reduce bleeding manifestations and improve the quality of life of chronic and persistent ITP children independent of its effect on the platelet count., (© 2022. The Author(s).)

Thrombopoietin receptor agonists are important therapeutic option in children with immune thrombocytopenia (ITP). We evaluated the response, efficacy, safety of a generic form of romiplostim manufactured in India for treating children with persistent/chronic ITP at our centre. Study of 45 children with persistent/chronic ITP was conducted of which 5 discontinued and 40 were included between 2019-2020. Patients received romiplostim for 20 weeks, at a dose of 5 mcg/kg/week. Platelet count at week 1, 3, 20 and 26 was assessed. Predesigned algorithm was used for dose adjustment. After 20 weeks, patients who had platelet count of 50 × 109/L or above were tapered off medication and monitored till 26 weeks. Median platelet count at enrolment was 11 x 109/L (IQR 23 X 109/L). 13/40 children had received >/= three lines of prior ITP therapy. Platelet response (platelet count rise to more than 50×109/L without rescue medications) observed in 26 (65%) patients at week 20. Rescue medication was used in 12/40 children. Sustained platelet response after tapering and stopping romiplostim observed in 22/40 children. No adverse events were considered serious or led to discontinuation of treatment. Our data demonstrated generic romiplostim is well tolerated and efficacious in children with persistent/chronic ITP., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

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: 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.

Myosin heavy chain 9 (MYH9)-related platelet disorders (MYH9-RD) belong to the group of inherited thrombocytopenias characterized by giant platelets and Döhle bodies. The process leading to the diagnosis of MYH9-RD in a 13-year-old male patient, followed by the diagnosis of chronic immune thrombocytopenic purpura (ITP), is described. The patient had thrombocytopenia with increased mean platelet volume since he was a little boy. Low CD41, CD42 and CD61 levels were detected in blood tests sent to complete missing diagnostic tests. Platelet aggregation tests were also abnormal. The requested genetic test revealed a heterozygous mutation in the MYH9 gene. The patient's audiogram and kidney functions were normal. In conclusion, because MYH9-RD appears to be rare, it is of great importance to maintain a high index of suspicion when managing patients diagnosed with chronic ITP. Additional complaints and findings should be considered at every outpatient clinic examination to make a more accurate diagnosis and prevent unnecessary treatments. [ABSTRACT FROM AUTHOR]

Pathogenesis of thrombocytopenia is heterogeneous and resistance to treatment is a great challenge. In this study, we reviewed the demographic features of thrombocytopenic Egyptian patients. We also analyzed the role of T cell in chronic immune cases. IL-12, IL-35, IL-17, and TGF-β were measured by ELISA. The median age at the time of diagnosis was 30 years and its range was 14-70. The median platelet count at the time of diagnosis was 15 × 109/L. Regarding treatment and follow-up, there was an indication for treatment in 96% of patients. Of the 150 ITP patients who were given first-line therapy (corticosteroid 1 mg/kg/day PO), there was a complete response (CR) in 40.3% while 59.7% patients were nonresponsive to therapy. Forty-five chronic cases fulfilled the criteria for cytokine assay. Comparison between the case group and the control group revealed statistically significant lower platelet count in cases, while the four measured cytokines were statistically significant higher in cases rather than the control. Correlation between the platelet count and the level of cytokines was statistically insignificant. The remission rate in ITP on steroid as first-line therapy is less than 50%. The higher expression of IL-12 and IL-35in chronic ITP is due to the persistently higher Th1 activity which explains the continuity of the disease, while the higher expression of Treg cytokines (IL-17 and TGF-β) may be explained by effect of immunosuppression or upregulation of the receptors on Treg cells. [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]

Aim: To describe the clinical course, morbidity and platelet recovery in an unselected Nordic cohort of children with chronic Immune Thrombocytopenic Purpura (ITP). Methods: Prospective 5-year follow-up of 96 children with ITP lasting more than 6 months, with reporting of hospital admissions, severity of bleeding episodes and stabilization of platelet counts above 20, 50 and 150 × 109/L. Results: The estimated 5-year recovery rate was 52%; exclusion of 12 splenectomized children did not change the estimate. Events eliciting admission to hospital occurred in 39 (41%). Major haemorrhages occurred in eight children (8%), including a nonfatal intracranial haemorrhage in one child (1%). The overall admission rate was 0.4/year of thrombocytopenia, decreasing during follow-up as thrombocytopenia converted to milder degrees. Early recovery within 2 years of diagnosis occurred in 35%, was associated with low morbidity and was more likely in young children with abrupt onset of symptoms. Conclusion: In a Nordic cohort of children with chronic ITP, one half had recovered 5 years after diagnosis, more than half never required hospitalization and <10% experienced serious bleeding episodes, always with a platelet count <20 × 109/L. Aggressive management can be restricted to the minority of children with continuing severe thrombocytopenia and frequent, clinically significant bleeding events. [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]

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]

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]

The objectives of this study were to investigate the effectiveness of oral megadose methylprednisolone (OMMP) therapy in children with chronic immune thrombocytopenic purpura (ITP). Twenty‐two patients were given oral methylprednisolone daily for 7 d (30 mg/kg for 3 d and then 20 mg/kg for 4 d). OMMP therapy was repeated once per month if the platelet count was less than 20,000/mm3 at the 30th day of therapy, for up to six courses. The number of platelets of all patients increased gradually during the OMMP therapy, with a peak number at the 7th day, then decreased until the 14th day, and remained relatively stable until 12 months. During the study no patient had a platelet count less than 20,000/mm3 at the 3rd day and 50,000/mm3 at the 7th day. Although the number of platelets was gradually decreased between the 7th and 14th days, it remained above 100,000/mm3 for at least 12 months in the nine patients, and above 20,000/mm3 in the four patients. None of these 13 patients required hospitalization or therapy during the follow‐up period. All of the patients tolerated the medication well. None of them reported side‐effects that were severe enough to discontinue therapy. We conclude that OMMP therapy is a safe, easy and effective therapy in children with refractory chronic ITP, and it may provide long‐term remission in about two thirds of the patients. [ABSTRACT FROM AUTHOR]