Risk Of Idiopathic Thrombocytopenic Purpura Research Articles

Vitamin D Insufficiency is Not Associated With Pediatric and Adolescent Immune Thrombocytopenia: A Study in Conjunction With its Receptor Genetic Polymorphisms.

Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous immunologic disorder. Vitamin D has immune-modulatory effects. The pleiotropic effects of vitamin D are exerted via vitamin D receptor (VDR) and its genetic alterations could influence its functions. In our study, we measured the serum 25-hydroxyvitamin D levels in 98 Pediatric and Adolescent ITP patients, in addition to 100 apparently healthy controls. Genetic polymorphisms of the VDR gene FokI, BsmI, ApaI, and TaqI were tested using specific restriction enzymes for each polymorphism. Vitamin D deficiency in the studied Pediatric age was a dominant factor, but it was found not to be associated with Pediatric ITP. However, patients carrying the FokI CC genotype had statistically higher vitamin D levels compared with those carrying other genotypes (P=0.036). Patients who were carriers of the BsmI G allele had a nearly 2-fold higher risk of ITP (odds ratio: 2.203; 95% confidence interval: 1.467-3.309). Therefore, the BsmI polymorphism of VDR could be considered a molecular risk factor for ITP.

Assessment of pre-specified adverse events following varicella vaccine: A population-based self-controlled risk interval study

BackgroundClinical trials and spontaneous reporting systems have revealed rare but biologically plausible adverse events following varicella immunization. Few post-marketing controlled studies have been conducted to assess the relationship between the varicella vaccine and these outcomes. ObjectivesTo evaluate the risk of pneumonia, idiopathic thrombocytopenic purpura (ITP), meningitis, encephalitis and ischemic stroke following varicella immunization. Materials and methodsThis nationwide observational study was based on Taiwan National Health Insurance data and National Immunization Information System from 2004 through 2014. Primary analysis included children aged 12–35 months who received the single varicella vaccine on the date of administration. The self-controlled risk interval design compared the incidence of pre-specified outcomes during a risk interval of 1–42 days post-vaccination and a control interval of 43–84 days. The outcomes of interest were defined as admitted pneumonia, ITP, meningitis, encephalitis, and ischemic stroke, as well as fracture as a negative control. Conditional Poisson regression was used to assess the incidence rate ratio (aIRR) with adjustments for age and seasonal effects. ResultsAmong 1,194,189 children, who receiving the varicella vaccine, there was no observed increase in the risk for ITP (aIRR 1.00; 95% CI, 0.76–1.33), meningitis (aIRR 1.21; 95% CI, 0.49–2.95), encephalitis (aIRR 1.00; 95% CI, 0.62–1.60), or ischemic stroke (aIRR 1.24; 95% CI, 0.31–4.95). A clustering feature with pneumonia occurred during days 36–42 post-vaccination (aIRR 1.10; 95% CI, 1.02–1.18). An increase in the risk for ITP was observed in children receiving the varicella and MMR vaccines concomitantly (aIRR 1.70; 95% CI, 1.19–2.43), but not among those receiving the varicella vaccine only. ConclusionsWe detected a small risk of incidental pneumonia associated with varicella vaccine in the 6th week after immunization. There was no increase in the risk of other pre-specified adverse events.

Bias and estimation under misspecification of the risk period in self‐controlled case series studies

The self-controlled case series (SCCS) method is useful for estimating the relative incidence (RI) of acute events, such as adverse events (AEs) during a specified risk period following an exposure (e.g., 6-week period after vaccinations or 30-day period after infection-related hospitalizations). In practice, the "optimal" risk period is unknown and must be specified. To date, two approaches are available to guide the specification of the risk period. Both methods do not fully utilize the nature of the bias due to misspecification, which to date has not been characterized. Thus, we elucidate the bias of SCCS estimate of the RI when the risk period is misspecified. We then propose a novel method that more effectively estimates the optimal risk period and the associated RI of AEs. The new method incorporates information on the functional form of the bias. Efficacy of the proposed approach is illustrated with substantial reduction in bias and variance in simulation studies. The proposed method is illustrated with two SCCS studies to determine the (1) risk of idiopathic thrombocytopenic purpura after measles-mumps-rubella vaccination in children and (2) risk of cardiovascular events after infection-related hospitalizations in older patients on dialysis.

CD16 and CD32 Gene Polymorphisms May Contribute to Risk of Idiopathic Thrombocytopenic Purpura.

BackgroundEpidemiological studies have evaluated the associations of CD16 158F>V and CD32 131H>R gene polymorphisms with the risk of idiopathic thrombocytopenic purpura (ITP).Material/MethodsPublished studies on CD16 158F>V and CD32 131H>R polymorphisms with susceptibility to ITP were systematically reviewed until April 1, 2014. The Cochrane Library Database, Medline, CINAHL, EMBASE, Web of Science, and Chinese Biomedical Database (CBM) were used to search for relevant studies and then a meta-analysis was conducted by using Stata 12.0 software in order to produce consistent statistical results.ResultsIn total, 10 clinical case-control studies with 741 ITP patients and 1092 healthy controls were enrolled for quantitative data analysis. Results of this meta-analysis suggest that CD16 158F>V polymorphism had strong correlations with the susceptibility to ITP under 5 genetic models (all P<0.05). However, no similar associations were found between CD32 131H>R polymorphism and the susceptibility to ITP (all P>0.05). Subgroup analysis by ethnicity revealed that CD16 158F>V polymorphism was associated with the increased risk of ITP among both Caucasian and non-Caucasian populations. Nevertheless, no statistically significant correlations between CD32 131H>R polymorphism and the risk of ITP were observed among Caucasians and non-Caucasians (all P>0.05).ConclusionsOur findings indicate that CD16 158F>V polymorphism may contribute to the increased risk of ITP, whereas CD32 131H>R polymorphism may not be an important risk factor for ITP.

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.

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.

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.

Post‐varicella thrombocytopenic purpura

The aim of the study was to characterize the clinical course of post-varicella idiopathic thrombocytopenic purpura (ITP) and to asses the risk of acquiring ITP after varicella infection. A retrospective study of all children diagnosed with ITP in a tertiary medical centre during 1998-2008. Findings were compared with the Intercontinental Childhood ITP Study Group database. The risk of acquiring ITP after a varicella infection was assessed. Ten children were diagnosed with post-varicella ITP. The incidence of post-varicella ITP was 1.9% amongst children diagnosed with ITP and 1.1% amongst children hospitalized for varicella. ITP was diagnosed, on average, 8.5 days after the onset of the varicella rash. The female-to-male ratio was 1:1.5. The average minimal platelet count was 9.5 × 10⁹ platelets/L. Post-varicella ITP had an acute course in 80% of cases and a chronic course in the remaining 20%. Bleeding episodes occurred in three patients. During the follow-up period, 11 patients with previously diagnosed ITP developed varicella. The infection had no apparent affect on the platelet count of the children with acute ITP, but caused a relapse in 71% of the patients with chronic ITP. Post-varicella ITP has similar clinical features and course to non-varicella associated ITP. The calculated risk of ITP as a complication of varicella infections is approximately 1:25,000.

Medical treatments for idiopathic thrombocytopenic purpura during pregnancy

Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder caused by immune-mediated thrombocytopenia. The magnitude of the maternal-fetal risk of ITP during pregnancy is controversial. Labour management of pregnant women with ITP remains controversial. Management of ITP during pregnancy is complex because of the disparity between maternal and fetal platelet counts. To assess the effectiveness and safety of corticosteroids, intravenous immunoglobulin, vinca alkaloids, danazol, dapsone, and any other types of pharmacological treatments for the treatment of idiopathic thrombocytopenic purpura during pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2009), LILACS (1982 to 8 February 2009), ClinicalTrials.gov (8 February 2009), Current Controlled Trials (16 February 2009), Google Scholar (16 February 2009) and ongoing and unpublished trials cited in the reference lists of relevant articles. Randomised controlled trials (RCTs) on any medical treatments for idiopathic thrombocytopenia purpura during pregnancy. Two review authors independently evaluated methodological quality and extracted trial data. Any disagreement was resolved by discussion or by consulting a third review author. This review included one RCT in which 38 women (41 pregnancies) were randomised, with only 26 women (28 pregnancies) being analysed.This RCT comparing the effect of betamethasone (1.5 mg/day) with no medication found no statistically significant difference in neonatal thrombocytopenia (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.62 to 2.05) and neonatal bleeding (RR 1.00, 95% CI 0.24 to 4.13). Review authors conducted an intention-to-treat analysis which showed similar findings: RR 1.18, 95% CI 0.57 to 2.45 and RR 1.05, 95% CI 0.24 to 4.61, respectively. Maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage were not studied by this RCT. Current evidence indicates that compared to no medication, betamethasone did not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy. There is insufficient evidence to support the use of betamethasone for treating ITP. This Cohrane review does not provide evidence about other medical treatments for ITP during pregnancy. This systematic review also identifies the need for well-designed, adequately powered randomised clinical trials for this medical condition during pregnancy. Unless randomised clinical trials provide evidence of a treatment effect and the trade off between potential benefits and harms are established, policy-makers, clinicians, and academics should not use betamethasone for ITP in pregnant women. Any future trials on medical treatments for treating ITP during pregnancy should test a variety of important maternal, neonatal or both outcome measures, including maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage.

DNMT3B 579G>T Promoter Polymorphism and the Risk for Idiopathic Thrombocytopenic Purpura in a Chinese Population

Epigenetics may influence the expression of numerous genes, which might contribute to autoimmune diseases. DNA methylation is mediated by DNA methyltransferases, especially DNA methyltransferase 3B (DNMT3B). Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between DNMT3B 579G>T and the risk for idiopathic thrombocytopenic purpura (ITP). The DNMT3B 579G>T polymorphisms were analyzed by PCR-RFLP. There was no significant difference in genotype and allele distribution between the ITP patient and the controls (p = 0.722 and 0.667, respectively). Similar results were observed between the 2 groups when stratified by age and disease course, including acute in childhood, chronic in childhood, acute in adult and chronic in adult. Importantly, this study showed a statistical difference in the distribution of SNP of DNMT3B between Chinese and Koreans or Americans. It is shown that the SNP of DNMT3B 579G>T may not be used on its own as a marker to predict the susceptibility to ITP in a Chinese population and that DNMT3B 579G>T promoter SNP varies from one ethnic population to another.

Single Nucleotide Polymorphism in DNMT3B Promoter and the Risk for Idiopathic Thrombocytopenic Purpura in Chinese Population

Epigenetic changes in gene expression, including DNA methylation and histone modifications, might contribute to autoimmunity. DNA methylation is mediated by a family of DNA methyltransferases. Polymorphisms of the DNA methyltransferase 3B (DNMT3B) gene may influence DNMT3B activity on DNA methylation, thereby modulating the susceptibility to some diseases. The purpose of this study was to investigate the association between the single nucleotide polymorphism (SNP) in promoter of the DNMT3B gene and the risk for development of idiopathic thrombocytopenic purpura (ITP). In this hospital-based case-control study, the DNMT3B SNP was genotyped in 201 patients with ITP and 136 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The C/C genotype was not detected in both the patients with ITP and the controls. In the controls, the frequencies of T/T and C/T genotypes and T and C alleles were 97.8%, 2.2%, 98.9%, and 1.1%, respectively. There was no significant difference in genotype and allele distribution between the patients with ITP and the controls (P = 0.745 and 0.747, respectively). No significant difference was observed in genotype and allele distribution between the two groups when stratified by the age. The similar results were shown among the four groups of patients with ITP: acute childhood, chronic childhood, acute adult, and chronic adult. This polymorphism was distributed similarly between the patients with ITP and the controls. It demonstrated that it may not be used as a stratification marker to predict the susceptibility to ITP, at least in the population of North China.

The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts.

No firm data are available on the natural history of idiopathic thrombocytopenic purpura (ITP) or on mortality rates or frequency of major bleeding episodes associated with this condition. The disease is thought to have a relatively benign course, despite the frequent occurrence of very low platelet counts. This prevailing conception often guides therapeutic decisions. To estimate the bleeding risk of ITP involving persistent low platelet counts (<30 x 10(9)/L) and its impact on prognosis. Age-adjusted bleeding risk was derived from a pooled analysis of ITP clinical series based on a systematic literature search. The risk estimate was incorporated into a Markov model to determine its impact on prognosis. Seventeen case series complied with inclusion criteria, including 1,817 patients with ITP. There were 49 cases of fatal hemorrhage over an estimated 1,258 to 3,023 patient-years at risk. The rate of fatal hemorrhage before age adjustment was estimated at between 0.0162 and 0.0389 cases per patient-year. Age-adjusted rates were 0.004, 0.012, and 0.130 cases per patient-year for age groups younger than 40, 40 to 60, and older than 60 years, respectively. Predicted 5-year mortality rates ranged from 2.2% for patients younger than 40 years to 47.8% for those older than 60 years. A 30-year-old woman remaining thrombocytopenic due to ITP was predicted to lose 20.4 years (14.9 quality-adjusted life years) of her potential life expectancy. At age 70, predicted loss was 9.4 years (5.0 quality-adjusted life years). Idiopathic thrombocytopenic purpura with persistent low platelet counts carries a grave prognosis. Therefore, an active therapeutic approach in the clinical management of affected patients should be considered. In view of the significant potential implications of the model results, we call for initiating a well-designed prospective inception cohort study of patients with ITP.