Childhood Idiopathic Thrombocytopenic Purpura Research Articles

Idiopathic Thrombocytopenic Purpura: Current Limitations and Management.

Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenia, is a blood disorder characterized by a reduction in the number of platelets. A reduction in the number of platelets beyond the normal levels leads to several consequences. A severe reduction in blood platelet levels leads to a rash of purple spots on the skin, joints, etc.due to leakage in the small blood vessels, easy bruising, bleeding gums, intestinal bleeding, and hemorrhage. Suppose a case of ITPresolves in fewer than six months. In that case, it is an acute case of ITP. Still, if a case settles in more than six months, it is a case of ITP. The cause of a reduced platelet count can be increased peripheral destruction or impaired production; this is termed an autoimmune condition in which the body's immune system attacks platelets thinking it to be a foreign antigen. ITP in children occurs commonly following a previous viral attack. Even though evaluating patients' reports is useful for understanding and guiding the treatment, these estimates might not be regularly evaluated in clinical settings. First-line drugs in the treatment of ITP are corticosteroids, and long-term use of these drugs has several side effects, such as excessive increase in weight, mental health disturbances, and sleep disturbances; additional therapies to treat hemorrhage are usually momentary. As a result, it is essential to recognize the flaws in current procedures and adopt innovative measures for the management and minimization of difficulties.

Variations of Redox Balance in Different Stages of Childhood Immune Thrombocytopenic Purpura.

Few previous studies indicated the role of oxidative stress in the pathogenesis of childhood idiopathic thrombocytopenic purpura (ITP), but there are little data regarding changes in redox balance in different forms of the disease, and changes after therapeutic procedures. We aimed to investigate the values of pro-oxidants and antioxidative capacity in various forms of ITP before and after the applying therapy. The research included 102 children, classified into the following groups: (1) newly diagnosed ITP (ndITP), (2) persistent ITP, (3) chronic ITP (chITP), and (4) control groups: (A) healthy control and (B) previously experienced ITP-healthy children who had been suffering from ITP earlier. During the clinical assessment, a blood sample was taken from the patients, from which the value of pro-oxidants (index of lipid peroxidation measured as TBARS, nitrites [NO2 -], as measurement of nitric oxide [NO] production, superoxide anion radical [O2 -], and hydrogen peroxide [H2O2]) and the capacity of antioxidant protection (activity of superoxide dismutase and catalase, and quantity of reduced glutathione) were determined spectrophotometrically. Our results demonstrated that values of pro-oxidants, especially reflected through the TBARS and O2 -, were the highest in the ndITP and exacerbated chITP groups. Also, the activity of the endogenous antioxidative defense system was the lowest in these groups. Intravenous immunoglobulin therapy in the ndITP group exerted the most prominent effect on the redox balance. It can be concluded that severity and exacerbation of the ITP are closely related to the redox status.

Prognosis and risk factors of chronicity in childhood idiopathic thrombocytopenic purpura: a single-center experience

Objective: In previous studies, chronicity risk factors for idiopathic thrombocytopenic purpura (ITP) are unclear. This study aimed to evaluate the outcome of children with ITP and determine the chronicity risk factors.
 
 Methods: This study retrospectively examined the demographics, laboratories, outcome, and chronicity risk factors among sixty children with ITP and obtained the data from the computer system. We analyzed demographics, treatment, and laboratory risk factors for chronic ITP by IBM SPSS and used binary logistic regression analysis.
 
 Results: Of 60 children with ITP, 32 (53.3%) had acute, 25 (41.7%) had chronic, and 3 (5%) had persistent ITP. Demographics, laboratories (age

Splenectomy

Laparoscopic splenectomy has become an established standard of care in the management of surgical diseases of the spleen, except in the hemodynamically unstable trauma patient requiring splenectomy. Although adoption of minimally invasive splenectomy has led to a gradual decrease in the indications for open splenectomy, both procedures are still essential components of spleen surgery. This review describes the indications and contraindications for procedure, preoperative preparation and consent, operative anatomy and technique, and long-term follow-up. Tables review the clinical indications for splenectomy, classification of splenectomy, a comparison of laparoscopic versus open postsplenectomy outcomes, indications and contraindications for partial splenectomy, and reported incidences of postoperative outcomes and complications after splenectomy. Figures depict splenomegaly, the American Society of Hematology 2011 evidence-based practice guidelines for management of primary idiopathic thrombocytopenic purpura in children and adults, a splenic mass, a splenic cyst, massive splenomegaly, laparoscopic splenectomy, the 2014 Centers for Disease Control and Prevention recommendations for adult and pediatric splenectomy vaccination, splenic artery embolization, various laparoscopic approaches to splenectomy, splenic vascularization, division of splenic artery branches, suspensory ligaments of the spleen, laparoscopic exposure and transection of splenic hilum, retrieval bags and related procedures, open splenectomy, stapling, and laparoscopic partial splenectomy. Videos demonstrate purely laparoscopic splenectomy and hand-assisted laparoscopic splenectomy. This review contains 26 figures, 5 tables, 2 videos, and 111 references.

The Role of Helicobacter Pylori Infection in Idiopathic Thrombocytopenic Purpura in Children

Background: Many studies had found obvious relation between helicobacter pylori infection and chronic idiopathic thrombocytopenic purpura; several studies have reported remission of immune thrombocytopenic purpura (ITP) after eradication of a coexistent Helicobacter pylori infection in adults, data in children are limited. Objective: To detect the association of H. pylori infection and idiopathic thrombocytopenic purpura in children and the effect of eradication of the infection on platelet count in these patients. Patients and methods: This study was conducted on 83 chronic idiopathic thrombocytopenic purpura children with age range from 3 to 13 years. They were 46 males 37 females. Also the study included 104 healthy individual with the same range of age. They were 58 males and 46 females as a control group. This was between October 2018 and September 2019 in the Pediatric Hematology and GIT Clinics or inpatients wards of Pediatric Department. Results: Clinical benefit occurred in 31 cases of the 83 chronic ITP (cITP) patients screened; nevertheless, we have a simple, inexpensive, non‐invasive screening method; the adverse events of eradication therapy are negligible, together with an affordable cost, all uncommon attributes among the specific treatments currently available for cITP; therefore it is worthwhile to test for and treat H. pylori infection. Conclusion: Our data showed a prevalence of H. pylori infection in cITP pediatrics that was similar to other studies. We found that successful H. pylori eradication induced platelet response in 37.3% of 83 cases included in our study.

The Role of Helicobacter Pylori Infection in Idiopathic Thrombocytopenic Purpura in Children

Background: Many studies had found obvious relation between helicobacter pylori infection and chronic idiopathic thrombocytopenic purpura; several studies have reported remission of immune thrombocytopenic purpura (ITP) after eradication of a coexistent Helicobacter pylori infection in adults, data in children are limited. Objective: To detect the association of H. pylori infection and idiopathic thrombocytopenic purpura in children and the effect of eradication of the infection on platelet count in these patients. Patients and methods: This study was conducted on 83 chronic idiopathic thrombocytopenic purpura children with age range from 3 to 13 years. They were 46 males 37 females. Also the study included 104 healthy individual with the same range of age. They were 58 males and 46 females as a control group. This was between October 2018 and September 2019 in the Pediatric Hematology and GIT Clinics or inpatients wards of Pediatric Department. Results: Clinical benefit occurred in 31 cases of the 83 chronic ITP (cITP) patients screened; nevertheless, we have a simple, inexpensive, non‐invasive screening method; the adverse events of eradication therapy are negligible, together with an affordable cost, all uncommon attributes among the specific treatments currently available for cITP; therefore it is worthwhile to test for and treat H. pylori infection. Conclusion: Our data showed a prevalence of H. pylori infection in cITP pediatrics that was similar to other studies. We found that successful H. pylori eradication induced platelet response in 37.3% of 83 cases included in our study.

Efficacy and Safety of Eltrombopag for the Treatment of Chronic Idiopathic Thrombocytopenic Purpura in Children and Adolescents

Background: Chronic ITP is a very common disease in children. Most treatment options have focused on slowing platelet destruction like corticosteroids and IVIG. These treatments are not always effective, or have only a transient effect, and treatment related adverse events often restrict further use. Impaired platelet production has been evolved as a potential disease mechanism for ITP. As a result, growth factor and growth factor analogue stimulation of megakaryopoiesis has also been investigated. Objective: is to evaluate the efficacy and safety of eltrombopag for the treatment of children and adolescents with chronic ITP. Subjects and methods: It was a prospective cohort study which was conducted on forty patients (22 males and 18 females) with chronic ITP. They were treated with eltrombopag for a period ranged from 6 months to 2 years after failure of first line of treatment (steroids, IVIG or both). Patients started eltrombopag with mean initial platelet count 14.4 X 103 / uL and were evaluated after at least 6 months of therapy. The study was approved by the academic and medical ethics committee of Zagazig University and a written informed consent was obtained from all patients. Results: Thirty patients (75%) responded to eltrombopag with a mean platelet count of 100.9 X103/ uL while 10 patients (25%) did not respond to the drug. Mean platelet count was significantly higher after eltrombopag therapy (100.9 ± 65.97 versus 14.4 ± 8.87, P < 0.001). The longer the duration of treatment, the higher the mean platelet count after treatment (r = 0.4, P < 0.001). Only 43.3% of responders received combined treatment with IVIG and steroids versus 20% of non-responders (p = 0.006). Conclusion: Eltrombopag is an effective, well tolerated and safe drug to restore platelet counts at levels high enough to prevent bleeding events in children with chronic ITP.

Efficacy and Safety of Eltrombopag for the Treatment of Chronic Idiopathic Thrombocytopenic Purpura in Children and Adolescents

Background: Chronic ITP is a very common disease in children. Most treatment options have focused on slowing platelet destruction like corticosteroids and IVIG. These treatments are not always effective, or have only a transient effect, and treatment related adverse events often restrict further use. Impaired platelet production has been evolved as a potential disease mechanism for ITP. As a result, growth factor and growth factor analogue stimulation of megakaryopoiesis has also been investigated. Objective: is to evaluate the efficacy and safety of eltrombopag for the treatment of children and adolescents with chronic ITP. Subjects and methods: It was a prospective cohort study which was conducted on forty patients (22 males and 18 females) with chronic ITP. They were treated with eltrombopag for a period ranged from 6 months to 2 years after failure of first line of treatment (steroids, IVIG or both). Patients started eltrombopag with mean initial platelet count 14.4 X 103 / uL and were evaluated after at least 6 months of therapy. The study was approved by the academic and medical ethics committee of Zagazig University and a written informed consent was obtained from all patients. Results: Thirty patients (75%) responded to eltrombopag with a mean platelet count of 100.9 X103/ uL while 10 patients (25%) did not respond to the drug. Mean platelet count was significantly higher after eltrombopag therapy (100.9 ± 65.97 versus 14.4 ± 8.87, P < 0.001). The longer the duration of treatment, the higher the mean platelet count after treatment (r = 0.4, P < 0.001). Only 43.3% of responders received combined treatment with IVIG and steroids versus 20% of non-responders (p = 0.006). Conclusion: Eltrombopag is an effective, well tolerated and safe drug to restore platelet counts at levels high enough to prevent bleeding events in children with chronic ITP.

Regulatory T cell CD4 ‏&CD25‏ expression and chemokine C-X-C ligand 13 level before and after corticosteroid therapy in pediatric ITP patients

Childhood Idiopathic thrombocytopenic purpura (ITP) is one of the most commons autoimmune bleeding disorders characterized by isolated, immune-mediated low platelet count, the T-follicular helper (Tfh) cells are a subset of effector CD4 (+) T cells, that plays a pivotal role in maintaining self-tolerance, deregulation of Tfh activities has a key role in immune process taking place in ITP in which the production of platelet autoantibodies might be caused by cytokine network dysregulation. The objective of our study was to analyze the relationship of Tfh cells CD4&CD25 and C-X-C ligand 13 (CXCL13) expressions before and after steroid thereby in pediatric ITP. Material and method: the study included 45 pediatric patients with acute ITP and 20 healthy controls; we used flowcytometry to assess percentages of CD4‏ and CD25‏ cells as markers of regulatory T cells, also, the serum level of interleukin- CXCL13 was measured by ELISA at diagnosis and after 4 weeks receiving corticosteroid. Results: the expression of CD4‏ & CD25‏ ‏ markers were significantly reduced in ITP cases, who also showed an elevated CXCL13 level in comparison to controls, however, the level of CXCL13 declined after treatment, the CXCL13 optimum cut off point for predicting ITP response to therapy was determined to be 90 pg/ml with AUC 0.976, Sensitivity 88.89% and Specificity 100% P-value < 0.00. Conclusion: Serum CXCL-13 levels could be used as a significant predictor of response to therapy in ITP patients, CD4&‏CD25 expression has a role in the pathogenesis of childhood acute ITP principally linked to the level of platelet count drop.

Childhood Idiopathic Thrombocytopenic Purpura: Oral Manifestations and Dental Care

Oral manifestations may be the first clinical signs of idiopathic thrombocytopenic purpura (ITP) diagnosed by a pediatric dentist. The aim of the present study was to describe oral manifestations and dental care for patients with ITP. A narrative review of the literature was performed, involving a search in the MEDLINE (PubMED) electronic database for relevant articles published in English using the following keywords:

Characteristics of functional somatic syndromes and bodily distress syndrome in the general Danish population–The DanFunD study

Childhood Idiopathic thrombocytopenic purpura (ITP) is one of the most commons autoimmune bleeding disorders characterized by isolated, immune-mediated low platelet count, the T-follicular helper (Tfh) cells are a subset of effector CD4 (+) T cells, that plays a pivotal role in maintaining self-tolerance, deregulation of Tfh activities has a key role in immune process taking place in ITP in which the production of platelet autoantibodies might be caused by cytokine network dysregulation. The objective of our study was to analyze the relationship of Tfh cells CD4&CD25 and C-X-C ligand 13 (CXCL13) expressions before and after steroid thereby in pediatric ITP. Material and method: the study included 45 pediatric patients with acute ITP and 20 healthy controls; we used flowcytometry to assess percentages of CD4‏ and CD25‏ cells as markers of regulatory T cells, also, the serum level of interleukin- CXCL13 was measured by ELISA at diagnosis and after 4 weeks receiving corticosteroid. Results: the expression of CD4‏ & CD25‏ ‏ markers were significantly reduced in ITP cases, who also showed an elevated CXCL13 level in comparison to controls, however, the level of CXCL13 declined after treatment, the CXCL13 optimum cut off point for predicting ITP response to therapy was determined to be 90 pg/ml with AUC 0.976, Sensitivity 88.89% and Specificity 100% P-value < 0.00. Conclusion: Serum CXCL-13 levels could be used as a significant predictor of response to therapy in ITP patients, CD4&‏CD25 expression has a role in the pathogenesis of childhood acute ITP principally linked to the level of platelet count drop.

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.

Evaluation of prevalence, clinical spectrum and outcome of acute ITP in children in a tertiary care centre in Odisha, India

Background: Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenic purpura is one of the commonest bleeding disorders encountered in children between the ages of 2 to 10 years affecting both sexes. The objectives of the study were to collect the prospectively data including age, gender, bleeding type, platelet count and other laboratory tests, treatments, responses to treatment and outcomes in children with acute ITP from 1month to 14 years of age over a period of two years.Methods: The present study was conducted in the Department of Paediatrics Shrirama Chandra Bhanj, Medical College and Hospital and Sardar Vallabhbhai Patel Post Graduate Institute of Paediatrics, Cuttack during the period October 2011-Septmber 2013.Results: Total 36 cases of hospitalized acute ITP patients were studied out of 29200 cases. Prevalence of acute ITP was found to be 12.3 per 10,000 of all hospitalized children above 1 month. Male children outnumbered female children by Ratio 1.2. Past history of URTI was present in 78% of cases. Petechaie/purpura was the universal presenting features followed by Oral / Gum bleeding in 67% of cases. 8% of patient experienced clinical bleeding requiring blood transfusion and platelet transfusion. Mean duration of Hospital stay was 6.34 days. Maximum number of Patients (69%) had complete recovery and 14% each had persistent and chronic course.Conclusions: ITP is a common pediatrics disease presenting at any age with low morbidity and mortality. Most children with acute ITP recover in weeks to months. A long-term hospital based prospective study is suggested to know any significant risk factor in patient presenting with acute ITP.

Analysis of HPA gene Polymorphisms in Children with Acute or Chronic ITP

To investigate the frequency distribution of human platelet antigen allele HPA-2 and HPA-15 among the pediatric patients with acute or chronic idiopathic thrombocytopenic purpura (ITP) in Chinese Guangxi area, and to explore the potential correlation of ITP with HPA-2 and HPA-15 gene polymorphisms. The clinical and laboratorial data of 46 children diagnosed as acute ITP and 46 children diagnosed as chronic ITP between January 2007 and December 2014 were collected. Genotyping of HPA-2 and HPA-15 in 92 ITP patients and 48 healthy controls was performed by using polymerase chain reaction (PCR) combined with direct sequencing. The allele frequencies of HPA-2 and HPA-15 were significantly different among the acute, chronic and control groups; the allele frequencies were significantly different between the chronic ITP group and the control group (P<0.0167), while the difference was not statistically significant between the acute and chronic ITP groups as well as between the acute ITP and the control group (P>0.0167). The gene polymorphism of HPA-2 and HPA-15 may correlate with the risk of chronic ITP, but may not correlate with acute ITP in children.

50 Years Ago in TheJournal ofPediatrics: Idiopathic Thrombocytopenic Purpura in Childhood

50 Years Ago in TheJournal ofPediatrics: Idiopathic Thrombocytopenic Purpura in Childhood

Dental considerations on the management of Idiopathic Thrombocytopenic Purpura in children: case report

Idiopathic Thrombocytopenic Purpura (ITP) is a hematological disease characterized by decreased number of blood platelets. Clinically, children with ITP may present petechiae, ecchymoses, haematuria, epistaxis and occasionally hemorrhage. Oral manifestations include spontaneous gingival bleeding, petechiae or hematomas of the mucosa, palate and tongue. It is important for dentists to be aware of ITP in order to properly recognize this condition and offer the adequate treatment to the patient. The aim of this report was, therefore, to relate the case of a 4-year-old patient with acute ITP, to review its main clinical signs in children and describe the management of these patients at the dental office.

Is Helicobacter pylori infection a risk factor for idiopathic thrombocytopenic purpura in children?

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder, which occurs as a result of autoantibodies attachment to the platelets surface and subsequent destruction. Several organisms can mimic features of human antigens (Ags) and induce autoantibody production. One of these organisms is Helicobacter pylori (HP). We assessed the prevalence and relationship of HP infection with ITP in a population of children. One hundred and six children younger than 18 years old were enrolled in this case-control study in which 42 children with ITP were in the case group and 64 healthy children were in the control group. Stool exam for detection of HP-Ag were performed and the variables were compared between the two groups. Mean ± standard deviation age of case and control group was 6.4 ± 3.4 and 8.6 ± 4.4 years old, respectively. HP stool Ag differ significantly between the case and the control groups (P < 0.05). Our results support the role of HP in ITP of children, and urea breath test or Ag detection of HP in stool of these patients is recommended.

Chronic immune thrombocytopenia in childhood

Chronic thrombocytopenias are pathological conditions defined as a persistent platelet count below the normal range for more than 6-12 months, clinically characterized by mucocutaneous bleeding. Recently, an International Working Group of expert clinicians has redefined standard terminology and definitions of primary and secondary chronic immune thrombocytopenia (ITP). A document issued on acute childhood idiopathic thrombocytopenic purpura (AIEOP) provides parents and physicians with guidelines for the management of chronic ITP and gives prominence to the periodic re-evaluation of differential diagnosis. The majority of chronic ITP children do not require pharmacological treatments, especially if symptoms are absent or minimal and the treatment decision depends on several factors, in particular clinical conditions rather than platelets count. The recommendations distinguish three therapeutic strategies: emergency or symptomatic treatment, maintenance therapy and treatment aiming at definitive remission. Experimental/off-label treatment of chronic ITP are reported in the literature, such as the use of rituximab. Currently, other drugs (thrombopoiesis stimulating factors, mycophenolate, dapsone, danazol, azathioprine, rFVIIa, cyclophosphamide, vinca alkaloids and cyclosporine) are recommended in special cases or trials.

Alterations in immune cell subsets and their cytokine secretion profile in childhood idiopathic thrombocytopenic purpura (ITP).

Immune thrombocytopenic purpura (ITP) is acquired autoimmune disease in children characterized by the breakdown of immune tolerance. This work is designed to explore the contribution of different lymphocyte subsets in acute and chronic ITP children. Imbalance in the T helper type 1 (Th1)/Th2 cytokine secretion profile was investigated. The frequency of T (CD3(+), CD4(+), CD8(+)) and B (CD19(+)) lymphocytes, natural killer (NK) (CD16(+) 56(+)) and regulatory T (T(reg)) [CD4(+) CD25(+high) forkhead box protein 3 (FoxP3)(+) ] cells was investigated by flow cytometry in 35 ITP children (15 acute and 20 chronic) and 10 healthy controls. Plasma levels of Th1 cytokines [interferon (IFN-γ) and tumour necrosis factor (TNF-α)] and Th2 [interleukin (IL)-4, IL-6 and IL-10)] cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of Treg (P < 0·001) and natural killer (NK) (P < 0·001) cells were significantly decreased in ITP patients compared to healthy controls. A negative correlation was reported between the percentage of T(reg) cells and development of acute (r = -0·737; P < 0·01) and chronic (r = -0·515; P < 0·01) disease. All evaluated cytokines (IFN-γ, TNF-α, IL-4, IL-6 and IL-10) were elevated significantly in ITP patients (P < 0·001, P < 0·05, P < 0·05, P < 0·05 and P < 0·001, respectively) compared to controls. In conclusion, our data shed some light on the fundamental role of immune cells and their related cytokines in ITP patients. The loss of tolerance in ITP may contribute to the dysfunction of T(regs). Understanding the role of T cell subsets will permit a better control of autoimmunity through manipulation of their cytokine network.

Quick Recertification Series

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