Chronic Idiopathic Thrombocytopenic Purpura Patients Research Articles

Hypermethylation of the FOXP3 gene regulates Tregs immunodysregulation in chronic idiopathic thrombocytopenic purpura.

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a breakdown of immune tolerance; in ITP, the body's immune system mistakenly attacks and destroys platelets. This study aims to investigate the role and underlying mechanisms of FOXP3 in chronic ITP. Flow cytometry was used to detect the proportion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in CD4+CD25+ T lymphocytes from 20 patients with chronic ITP (CITP), 20 acute ITP (AITP) controls, and 20 healthy individuals.CD4+CD25+ Treg cells were isolated from peripheral blood of patients with CITP using magnetic beads and then treated with phosphate-buffered saline solution or decitabine (a methylation inhibitor) for 48 h. The levels of interleukin-2 (IL-2), IL-10, and transforming growth factor-beta1 (TGF-β1) in the plasma and CD4+CD25+ Treg cells were assessed by Enzyme-linked-immunosorbent serologic assay and quantitative real-time polymerase chain reaction (qRT-PCR). FOXP3 level was measured by qRT-PCR and Western blot analysis. Methylation-specific PCR (MS-PCR) was adopted to detect the status of FOXP3 methylation. The number of Treg cells and the contents of IL-2, IL-10, and TGF-β1 decreased in patients with CITP, compared to the AITP control group and normal group. FOXP3 expression was reduced and FOXP3 methylation increased in patients with CITP, compared to the AITP control group and normal group. Hypermethylation of FOXP3 promoter led to decrease in FOXP3 level in Treg cells. Inhibition of FOXP3 promoter hypermethylation promoted the secretion of IL-2, IL-10, and TGF-β1 in Treg cells. The number of Treg cells in CITP patients decreased, and the hypermethylation of FOXP3 promoter led to reduction of its expression in Treg cells, thus affecting the immune functioning of Treg cells.

Investigating Platelet Count in Children With Chronic Idiopathic Thrombocytopenic Purpura

Objectives: Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disease associated with immune dysregulation and autoantibody production. Numerous studies have shown that vitamin D has a protective effect against autoimmune diseases. As vitamin D deficiency has been identified in the majority of children with chronic ITP, this study evaluates the effects of vitamin D supplementation on the platelet count of such children. Methods: This was a quasi-clinical trial study and the study population consisted of children with chronic ITP who were referred to Afzalipur Hospital in Kerman City, Iran, from August 2020 to September 2021. All patients' vitamin D levels were measured and subjects with levels below 30 mg/dL were treated while the remaining children received the standard vitamin D supplementation. Subsequently, after a 3 and 9-month interval, patients’ vitamin D levels and platelet counts were assessed. Results: As a result, the mean serum vitamin D level increased significantly from 21.34±5.87 mg/dL to 34.25±5.64 mg/dL throughout the study. The mean serum platelet count was 18085.71±1292.10 µL at the start of the trial, 26628.57±1727.72 µL after 3 months, and 32114.28±1127.77 µL after 9 months, which showed a significant increase. Discussion: In conclusion, vitamin D boosts platelet count in chronic ITP patients. Thus, all children with chronic ITP should be evaluated and treated for vitamin D insufficiency.

Impact of target-mediated drug disposition on hetrombopag pharmacokinetics and pharmacodynamics in Chinese healthy subjects and patients with chronic idiopathic thrombocytopenic purpura.

The pharmacokinetics (PK) of hetrombopag were found to be nonlinear across evaluated dose ranges. The aim of this study was to develop a mechanism-based population pharmacokinetic/pharmacodynamic (PopPK/PD) model and to provide a reasonable expected therapeutic dose for a future confirmatory clinical study of hetrombopag. Nonlinear mixed-effects modelling was performed using pooled 2168 hetrombopag concentrations and 1526 platelet counts from 72 healthy subjects and 32 chronic idiopathic thrombocytopenic purpura (ITP) patients from two phase I studies and one phase II study. The final model was evaluated via goodness-of-fit plots, visual predictive check and nonparametric bootstrap. Simulations from the validated PopPK/PD model were used to devise an expected therapeutic dose for later confirmatory clinical study. The pharmacokinetic data of hetrombopag were well described by a modified target-mediated drug disposition (TMDD) model with dual sequential first-order absorption. Mean parameter estimates (interindividual variability) were CL/F 7.66 L/h (63.5%), Vc /F 30.0L (77.2%) and Kdeg 0.693/h (87.1%). The pharmacodynamic profile was well described by a five-compartment lifespan model with four-transit and one-platelet compartments. Simulation results suggested that chronic ITP patients following 10mg once-daily hetrombopag would able to achieve an ideal platelet count level (50-200 × 109 /L). TMDD was the primary reason leading to nonlinear PK profile of hetrombopag. Our PK/PD modelling and simulation results support 10mg once-daily as the recommended therapeutic dose for chronic ITP patients in subsequent confirmatory clinical study of hetrombopag.

Thiol / disulfide balance and oxidative stress parameters in pediatric patients diagnosed with acute and chronic idiopathic thrombocytopenic purpura.

Changes in oxidative stress and thiol / disulfide balance are thought to play a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Our study investigates total oxidant level (TOS), total antioxidant level (TAS), oxidative stress index (OSI) levels and thiol / disulfide balance in pediatric patients with acute and chronic ITP. Thirty four patients with acute ITP, eighteen patients with chronic ITP and thirty three healthy children (control) were included. TOS, TAS, OSI, thiol / disulfide balance were analyzed. In acute ITP, TAS levels were lower than chronic ITP and control, TOS and OSI levels were higher than control, and native thiol level was lower than chronic ITP (p < 0.05). In acute ITP; disulfide level, disulfide / native thiol and disulfide / total thiol ratios were higher than chronic ITP and control, and native thiol / total thiol ratio was lower than chronic ITP and control group (p = 0.038, p = 0.018, respectively). TOS and OSI levels of the chronic ITP were higher than the control group (p < 0.05). The results of this study have shown that oxidative stress increases in children with acute ITP and chronic ITP, that thiol / disulfide balance is disrupted in favor of disulfide in acute ITP, and that thiol / disulfide balance isn`t disrupted in chronic ITP patients whose platelet count is close to normal and who don`t require treatment.

First‐in‐patient study of hetrombopag in patients with chronic idiopathic thrombocytopenic purpura

BackgroundIdiopathic thrombocytopenic purpura (ITP) especially refractory and (or) relapsed ITP, is a serious and global health burden and its clinical treatment is far from being satisfied. Hetrombopag is a novel, small‐molecule thrombopoietin receptor agonist for the treatment of chronic idiopathic thrombocytopenic purpura (CITP). ObjectivesThis first‐in‐patient study aimed to investigate the safety, pharmacokinetics, and anticipated therapeutic dose of hetrombopag in CITP patients. MethodsIn this multicenter, first‐in‐patient study, CITP patients received hetrombopag in a dose escalation (2.5 mg/day, 5 mg/day, or 7.5 mg/day) cohort. All patients received hetrombopag in fasting condition once daily for 2 weeks. ResultsOf 44 patients screened, 32 were enrolled and treated. Most adverse events were graded 1 to 2 (ie, mild to moderate), and the incidence and severity were similar for three study cohorts. The pharmacokinetics of hetrombopag were found to be nonlinear with greater than dose‐proportional: 12.5% of patients (1/8) in the 2.5 mg/d cohort, 58.3% of patients (7/12) in the 5 mg/d cohort, 66.7% of patients (8/12) in the 7.5 mg/d cohort reached the primary study endpoint of a platelet count exceeding 50 × 109/L on day 28. ConclusionHetrombopag was well tolerated and preliminarily efficacious. Efficacy, safety, and pharmacokinetic data suggest that 7.5 mg hetrombopag once daily was the anticipated therapeutic dose of hetrombopag in CITP patients and has been recommended for investigation in a later confirmatory clinical study of hetrombopag.

Analysis of Differentially Expressed Genes and the Interaction Network between Acute and Chronic Idiopathic Thrombocytopenic Purpura in Children

Objective To analyze the differentially expressed genes and key proteins in T cells between acute and chronic idiopathic thrombocytopenic purpura (ITP) in children and provide the basis for the prevention and therapies of this disease. Methods Microarray gene chip data from T cells of children with acute or chronic ITP were downloaded from the GEO Database. The gene expression profiles,gene function,and protein interaction network were analyzed by R,QOE,Networkanalyst,GCBI,and GenClip. Results The gene expression profiles between these two groups were significantly different. Among the 54 675 genes analyzed,there were 457 (0.84%) differentially expressed genes between these two groups. In the protein interaction networks among top 20 differentially expressed genes,the core was JUN(down-regulated) and ITCH(up-regulated),which were both related to the tumor necrosis factor signaling pathway;differentially expressed genes were mainly related to the activation and tolerance of T cell. Conclusions The gene expression profiles differ between acute and chronic ITP patients,suggesting that the gene transcription profile plays a regulatory role in the different stages of ITP. JUN and ITCH may play a role in predict the progression of ITP and may exert their biological functions by regulating the tumor necrosis factor signaling pathway.

Platelet count response to Helicobacter pylori eradication for idiopathic thrombocytopenic purpura in northeastern Brazil.

BackgroundSeveral studies have demonstrated that platelet counts in Helicobacter pylori-positive patients with chronic idiopathic thrombocytopenic purpura improved significantly after successful eradication of the infection. However, depending of the geographical region of the study the results have been highly divergent.ObjectiveThe purpose of this study was to evaluate the effect of H. pylori eradication therapy on platelet count in a cohort of chronic idiopathic thrombocytopenic purpura patients from northeastern Brazil.MethodH. pylori status was determined in 28 chronic idiopathic thrombocytopenic purpura patients using the rapid urease test and histology. H. pylori-positive patients received standard triple therapy for one week. The effect of the eradication therapy was evaluated using the 13C-urea breath test two to three months after treatment.ResultsThe prevalence of H. pylori infection was similar to that found in the general population. Twenty-two patients (78.5%) were H. pylori-positive. Fifteen were treated, 13 (86%) of whom successfully. At six months, 4/13 (30%) displayed increased platelet counts, which remained throughout follow-up (12 months). Platelet response was not associated to mean baseline platelet count, duration of chronic idiopathic thrombocytopenic purpura, gender, age, previous use of medication, or splenectomy.ConclusionsH. pylori eradication therapy showed relatively low platelet recovery rates, comparable with previous studies from southeastern Brazil. The effect of H. pylori eradication on platelet counts remained after one year of follow-up suggesting that treating H. pylori infection might be worthwhile in a subset of chronic idiopathic thrombocytopenic purpura patients.

DNA methyltransferase 3B gene promotor and interleukin-1 receptor antagonist polymorphisms in Egyptian children with immune thrombocytopenic purpura

Background and objectives Idiopathic thrombocytopenic purpura (ITP) is an autoimmune condition characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. Many gene polymorphisms have been reported to be closely associated with the susceptibility to ITP. Aim of the work The current study aimed to investigate the association between the DNA methyltransferase DNMT3B-46359 C/T promoter and IL-1Ra polymorphism and the risk for acquisition of pediatric ITP in a cohort of Egyptian children. Patients and methods Genotyping of the studied genes using PCR-RFLP assays was conducted on 40 children with ITP and 20 age-matched and sex-matched normal controls. Results Our results revealed that DNMT3B-46359 C/T heterotype was higher in patients than in controls but did not reach statistical significance and conferred 2.2-fold increased risk for ITP (odds ratio=2.2, confidence interval = 1.4–2.6). There was no statistically significant difference between ITP patients and controls as regards allele frequency. Moreover, there was no statistically significant difference in the clinical and laboratory data between ITP patients with wild or mutant genotypes. Moreover, there was no statistically significant difference in the distribution of DNMT3B-46359 . C/T genotypes between acute and chronic ITP patients. Conclusion This genetic polymorphism cannot be considered as a molecular marker for ITP risk among Egyptian children. Moreover, it is not a molecular predictor for chronicity.

Eradication of Gastric Infection by Helicobacter pylori and Chronic Idiopathic Thrombocytopenic Purpura Situation

Background: Chronic idiopathic thrombocytopenic purpura (CITP) is an autoimmune disease with low platelet count and potentially bleeding tendency. Although autoimmune mechanisms play a crucial role in the disease yet in 20% of cases underlying diseases such as Helicobacter pylori (HP) infection can be involved. Objectives: The aim of this study was to evaluate effects of H. pylori eradication therapy on platelet count in CITP patients with H. pylori infection. Patients and Methods: During this clinical trial, performed from September 2011 to August 2012, twenty-three patients with CITP were divided in two groups, including one group with H. pylori infection and the other without infection. After determination of baseline platelet count in the two groups, patients with H. pylori infection underwent eradication therapy. Both groups were followed up for six months and platelet counts were checked at one-month intervals and finally, changes in platelet counts were statistically compared before and after treatment and also between the two groups. Results: From a total of 23 patients with CITP, 43% (10) of the cases were H. pylori positive and after eradication therapy, eight patients (80%) were successfully treated. Helicobacter pylori eradication therapy causes a statistically significant difference between the mean platelet count before and after HP eradication therapy. Conclusions: Helicobacter pylori infection has a significant effect on platelet count in patients with CITP and H. pylori eradication therapy should be considered as an important factor in platelet count recovery in CITP patients.

Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.

Correlation of Breg with CD4(+)T cells of peripheral blood in patients with CITP and its clinical significance

This study was aimed to detect the level of the peripheral blood Breg and CD4(+) T cell subgroups in patients with chronic idiopathic thrombocytopenic purpura (CITP) before and after therapy, and to analyse the charge of related cytokines and their correlation, to explore their roles in the pathogenesis of CITP. A total of 35 CITP cases were taken as the research group and 35 healthy persons were served as the control group. The peripheral blood mononuclear cells (PBMNC) were separated, the percentages of Th1, Th17, Th22 and Breg cells were detected by flow cytometry before and after treatment of glucocorticoid, and the IFN-γ, IL-17, IL-22 and IL-10 levels from PBMNC culture supernatant also were determined by ELISA. The results showed that there was significant difference as compared with the healthy controls, the proportion of peripheral blood Th1, Th17, Th22 cell subgroups all increased in CITP patients before treatment with glucocorticoid, the regulatory B cells (Breg) ratio was reduced, the differences had statistical significance (P < 0.05), but the differences were no statistically significant after treatment with glucocorticoid (P > 0.05). The levels of IFN-γ, IL-17, IL-22 from culture supernatant all increased in CITP patients before treatment, the level of IL-10 was lower than that of the healthy control, the difference was statistically significant (P < 0.05), but the there were no statistically significant differences after treatment (P > 0.05). There were positive correlation between the Breg cells and IL-10 expression in CITP patients (P < 0.05), the Breg cells and Th1, Th17, Th22 cells showed a negative correlation, IL-10 and IFN-γ, IL-17, IL-22 levels also showed a negative correlation. It is concluded that the down-regulation of regulatory B cells proportion and the IL-10 level may participate in the mechanism of CD4(+) T cell immunity disorder in CITP, which can provide new targets and ideas for the clinical immune regulation therapy.

Prevalence and Clinical Significance of Antithyroid Antibodies in Children with Immune Thrombocytopenic Purpura

Background and objective: To determine the prevalence and the clinical significance of thyroid autoantibodies and their influence on treatment response in children with idiopathic thrombocytopenic purpura (ITP). Patient and Method: We retrospectively analyzed the antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies from the records of 151 ITP patients who were admitted to the Pediatric Hematology Department of Gaziantep University between 2009 and 2012. Results: Anti-TPO and/or anti-TG was found positive in 38 (36.8%) of 103 patients whose thyroid autoantibody levels were measured. The comparison of positivity ratios of autoantibodies between acute and chronic ITP patients showed no significant difference. However, the separate comparison of each group of ITP patients with control group showed significantly high positivity ratios of autoantibodies in ITP patients. The initial mean platelet count of anti-TPO positive patients at diagnosis was significantly less than that of the negative patients (P = .008). One month after treatment, platelet count of anti-TPO positive patients was significantly less than that of the negative patients (P = .01). Moreover, the mean platelet counts of anti-TPO positive patients were significantly less than those of the negative patients after intravenous immunoglobulin treatment (P < .001). Conclusion: We demonstrated that the thyroid-autoimmune-diseases-related autoantibodies are frequently found in childhood ITP. Although no recommendation is found in international guidelines regarding screening for thyroid autoantibodies in patients with ITP, in view of the high incidence of antithyroid antibodies and their potential negative effect on treatment response, screening these patients for such antibodies would be recommended.

DNA methyltransferase 3B (DNMT3B − 579 G > T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. The present study aimed at exploring a novel molecular determinant that may influence the susceptibility and course of ITP in Egyptian children. To achieve our aim, genotyping of DNMT3B −579G>T promotor polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP patients and 150 age and gender matched healthy controls. The results obtained revealed that DNMT3B −579 TT homotype was significantly higher in ITP patients and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73–5.79). There was no statistically significant difference between ITP patients with wild or mutant genotypes as regards their clinical or laboratory data. Furthermore, there was no statistical difference in the distribution of DNMT3B −579G>T genotypes between acute and chronic ITP patients. In conclusion, DNMT3B −579G>T promotor polymorphism represents a novel genetic risk factor for ITP but not a predictor for tendency to chronicity in pediatric ITP in Egypt.

A Multi-Centre, Single-Arm, Open-Label Study Evaluating the Safety and Efficacy of Fixed Dose Rituximab in Patients with Refractory, Relapsing or Chronic Idiopathic Thrombocytopenic Purpura (R-ITP1000 Study) and Exploring Rituximab Response with the FcGammaR3A Polymorphisms

Abstract 1157▪▪This icon denotes a clinically relevant abstract Background:Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by low platelet count and mucocutaneous bleeding. Approximately 25–30% of adult patients with acute ITP develop chronicity; 30% of chronic ITP patients become refractory to corticosteroids and require additional therapy. As B-cells play an important pathophysiological role in autoimmune disease, rituximab, a chimeric anti-CD20 monoclonal antibody which depletes CD20+ B-cells has been used in chronic ITP. A dosing regimen based on lymphoma therapy (375 mg/m2 weekly × 4) has shown efficacy (∼38% Overall Response Rate-ORR) in adults in this context. Whether this schedule is optimal in autoimmune disease, in which the burden of pathological B-cells is low, is unknown. In this study we explored an abbreviated rituximab schedule, consistent with the approved rheumatoid arthritis dosing. We also explored inherited polymorphisms in FcGammaR3A (FCGR3A) as it has been shown to correlate with response to rituximab. AIM:The primary objective of this study was to determine the ORR, at week 8, among adults (≥ 18 years) with chronic or relapsing ITP (platelet count > 10 × 109/L and ≤ 50 × 109/L) according to the ASH guidelines, who received rituximab 1000 mg intravenous (IV) on days 1 and 15. A laboratory sub-study investigated the relationship between the FCGR3A-V/F158 polymorphisms and response to rituximab. METHOD:Patients received planned doses of rituximab and were followed-up for a minimum of 12 weeks. Assessments and procedures at mandatory follow-up visits occurring on weeks 8, 12, 26, 39 and 52 included physical examination, vital signs, FBC and serum chemistry. ORR was defined as the proportion of patients achieving a Complete Response (CR, platelet count > 150×109/L) or Partial Response (PR, > 50 × 109/L) at weeks 8 and 12 with 2 consecutive measurements, confirmed at least 2 weeks apart. Simon’s 2-stage design was used to determine if the ORR was more likely to be ≤ 38% or ≥ 50%. At least 50 out of 108 responders (46%) were required to conclude, with 95% confidence and 80% power, that the ORR was likely to be ≥ 50%. FCGR3A-V/F158 genotyping was performed using allele specific polymerase chain reaction (PCR) techniques previously described (Koene HR, et al. Blood 1997;90:1109–1111). Distribution of polymorphisms was correlated according to response rate, as pre-defined in the study protocol and the frequencies compared using the standard chi-squared test for independence via contingency table analysis. Results:Out of the 124 patients recruited, 2 did not receive study medication and 14 did not have a platelet count ≤ 50 × 109/L within 7 days of first rituximab dose and were excluded from analysis. At week 8, the confirmed ORR was 44% (47/108 patients); 9% and 34% of whom achieved CR and PR respectively. At week 12, 9 patients had a missing platelet count value and therefore response rate data was available for 99 patients; ORR=46% (45/99). Treatment was well tolerated with no safety signals reported. Genotyping data was available for 87 patients. Correlations between FCGR3A-V/F158 polymorphisms and response to rituximab showed that 32% (16/50) non-responders [minor or no response] and 19% (7/37) responders [CR or PR] were homozygous for the FCGR3A-F/F158 genotype; p=0.21. Conclusion:The ORR is comparable with published studies using a more frequent rituximab schedule. Although not statistically significant, non-responders were more likely to be homozygous for the FCGR3A-F/F158 genotype than responders. Further investigations are warranted to determine whether the same response can be achieved with single/lower dosing rituximab, if longer/ more intense dosing might improve ORR and if maintenance rituximab may improve durability of responses. Disclosures:Thurley:ROche Products Australia: Employment.

The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor-beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura

To increase our understanding of the etiology of idiopathic thrombocytopenic purpura (ITP) some cytokine gene polymorphisms were analyzed for susceptibility to the disease. The aim of this study was to investigate the role of tumor necrosis factor-alpha (TNF-α) -308 G/A and transforming growth factor-beta 1 (TGF-β1) -915 G/C polymorphisms in the development and clinical progression of childhood ITP. In all, 50 pediatric patients with ITP (25 with acute ITP and 25 with chronic ITP) and 48 healthy controls were investigated via LightCycler® PCR analysis for TNF-α -308 G/A and TGF-β1 -915 G/C polymorphisms. The frequency of TNF-α -308 G/A polymorphism was 20%, 16%, and 22.9% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The frequency of TGF-β1 -915 G/C polymorphism was 16%, 8%, and 8.3% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The risk of developing ITP and clinical progression were not associated with TNF-α -308 G/A (OR: 0.738, 95% CI: 0.275-1.981, and OR: 0.762, 95% CI: 0.179-3.249) or TGF-β1 -915 G/C (OR: 1.5, 95% CI: 0.396-5.685, and OR: 0.457, 95% CI: 0.076-2.755) polymorphisms. The frequency of TNF-α -308 G/A and TGF-β1 -915 G/C polymorphisms did not differ between pediatric ITP patients and healthy controls, and these polymorphisms were not associated with susceptibility to the development and clinical progression of the disease.

TPO receptor agonist for chronic idiopathic thrombocytopenic purpura.

Chronic idiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disorder that is characterized predominantly by a low platelet count. Thrombopoietin (TPO) receptor agonists increase production of platelets by stimulating the TPO receptor in people with chronic ITP. To determine the efficacy and safety of TPO receptor agonists in chronic ITP patients. We searched MEDLINE (from 1950 to March 2011), EMBASE (from 1974 to March 2011), and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3) to identify all randomized trials in chronic ITP. We also contacted authors of included studies and TPO receptor agonists manufacturers. Randomized controlled trials (RCTs) comparing TPO receptor agonists alone, or in combination with other drugs, to placebo, no treatment, other drugs, splenectomy or another TPO receptor agonist in patients with chronic ITP. Two review authors independently screened papers, extracted data and assessed the risk of bias in the included studies. Six trials with 808 patients were included. Five studies compared TPO receptor agonists with placebo (romiplostim: 100, eltrombopag: 299, placebo: 175); one study compared TPO receptor agonists with standard of care (SOC) (romiplostim: 157; SOC: 77). SOC included a variety of therapies, such as glucocorticoid, anti-D immune globulin, intravenous immune globulin, rituximab, azathioprine, and so on. Overall survival, one of our primary outcomes, was not studied by these RCTs and we could not estimate number needed to treat (NNT). Another primary outcome, improving significant bleeding events, did not reveal any significant differences between the TPO receptor agonists group and the control group (placebo or SOC) (versus placebo risk ratio (RR) 0.48, 95% confidence interval (CI) 0.20 to 1.15; versus SOC RR 0.49, 95% CI 0.15 to 1.63).For secondary outcomes, TPO receptor agonists statistically significantly improved overall platelet response (versus placebo RR 4.06, 95% CI 2.93 to 5.63; versus SOC RR 1.81, 95% CI 1.37 to 2.37), complete response (versus placebo RR 9.29, 95% CI 2.32 to 37.15) and durable response (versus placebo RR 14.16, 95% CI 2.91 to 69.01). There was a significant reduction in overall bleeding events (WHO grades 1 to 4) when compared to placebo (RR 0.78, 95% CI 0.68 to 0.89), but not when compared to SOC(RR 0.97, 95% CI 0.75 to 1.26).Total adverse events (Grades 1 to 5) were not statistically significantly different between the treatment and control groups(both placebo and SOC) (versus placebo RR 1.04, 95% CI 0.95 to 1.15; versus SOC RR 0.97, 95% CI 0.75 to 1.26). Total serious adverse events (Grade 3 and higher adverse events) were increased when patients receiving treatment with SOC (RR 0.61, 95% CI 0.40 to 0.92), but not receiving treatment with placebo (RR 0.92, 95% CI 0.61 to 1.38).There are selective and performance biases because of open-label and inadequate allocation. There was currently no evidence to support that TPO receptor agonists are effective in chronic ITP. Compared to placebo or SOC, despite significantly increased platelet response, there was no evidence to demonstrate that TPO receptor agonists did improve significant bleeding events in chronic ITP. The effect on overall survival awaits further analysis. Although long-term studies are lacking, current data demonstrated adverse effects of TPO receptor agonists were similar to that of placebo and SOC.

B Cell Activating Factor Gene Polymorphisms in Patients With Risk of Idiopathic Thrombocytopenic Purpura

IntroductionB cell activating factor (BAFF) is a ligand belonging to the tumor necrosis factor family and has an important role in B cells development, survival, and immunoglobulin-production. This study was aimed to study the association between haplotypes in the 5′ regulatory region of the BAFF gene and susceptibility to idiopathic thrombocytopenic purpura (ITP). MethodsBAFF gene polymorphisms expression at positions (−871C>T, −2701 T>A and −2841T>C) of 5′ regulatory region were determined with polymerase chain reaction restriction fragment length polymorphism technique in 40 chronic (ITP) patients and in 50 age- and sex-matched normal volunteers as a control group. ResultsThe difference between chronic ITP patients and control subjects as regards −871C>T polymorphism expression was highly statistically significant with higher expression of T allele in ITP patients than control group (P < 0.001). However, the other 2 polymorphisms did not show significant difference between the 2 groups. −871C>T polymorphism was associated with increased risk of chronic ITP with an odds ratio 18.857; however, the other 2 polymorphisms were not associated with an equivalent effect. Conclusion−871C>T BAFF gene polymorphism expression had a significant association with chronic ITP disease.

Effects ofHelicobacter pylorieradication in patients with immune thrombocytopenic purpura

BackgroundThe relationship between Helicobacter pylori (H. pylori) infection and chronic idiopathic thrombocytopenic purpura (ITP) has been confirmed; however, no clear evidence for the effectiveness of H. pylori eradication on ITP exists thus far. The purpose of this study was to investigate platelet recovery in chronic ITP after H. pylori eradication.MethodsA total of 25 patients (18 male, 7 female; the median age of 55 years) diagnosed with ITP, whose platelet counts were less than 100×103/µL, were enrolled. They were tested for H. pylori infection by the rapid urea test or urea breath test. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection.ResultsOf the 25 patients, 23 (92%) were diagnosed with H. pylori infection. Of all the ITP patients, 11 (44%) exhibited a complete response (CR) to H. pylori eradication therapy; 6 (24%), a partial response (PR); and 8 (32%) were nonresponsive (NR). Predictive factors of response after H. pylori eradication therapy were platelet counts at the initial response (27.3% responders among patients with platelet counts <100×103/µL vs 100% responders among patients with platelet counts ≥100×103/µL, P<0.001) and H. pylori infectivity (73.9% responders among the H. pylori positive patients vs 0% responders among the H. pylori negative patients, P=0.032).ConclusionThis study confirmed the efficacy of H. pylori eradication in increasing the platelet count in ITP patients. Further studies with a larger number of patients are necessary to identify the crucial predictive factors responsible for platelet recovery in chronic ITP patients with the H. pylori infection.

Does Helicobacter Pylori Play A Role in the Pathogenesis of Childhood Chronic Idiopathic Thrombocytopenic Purpura?

Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10–15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×109/L) or partial (platelet count between 50 and 150×109/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.

Validity of a procedure to identify patients with chronic idiopathic thrombocytopenic purpura in the Danish National Registry of Patients

Administrative data may be useful for epidemiological studies of chronic idiopathic thrombocytopenic purpura (ITP). However, the quality of the recorded diagnoses needs evaluation. We evaluated the validity in predicting chronic ITP of the International Classification of Diseases (ICD)-10 diagnoses of ITP in the Danish National Registry of Patients (NRP). We used the NRP to identify patients with ITP, according to code D69.3, from January 1, 1996 to December 31, 2007. We defined chronic ITP as lasting longer than 6 months by including only patients with 2 or more hospital ITP diagnoses over longer than 6 months. We confirmed diagnoses by evaluating each candidate chronic ITP patient's medical chart and estimating the positive predictive value (PPV) and 95% confidence interval (CI) of the recorded NRP diagnostic code. We identified 513 patients with chronic ITP in the NRP. We were able to retrieve the charts of 439. After evaluation of the charts, 410 patients were deemed to have a valid diagnosis of chronic ITP, yielding a PPV of 0.93 (95% CI: 0.91-0.96). The validity of this procedure to identify chronic ITP patients was high. The NRP is valid for epidemiological studies of patients with chronic ITP.