Previous guidelines for the treatment of immune thrombocytopenia (ITP) have traditionally focused on a dichotomy between pediatric and adult ITP. Adolescents and young adults (AYAs) do not neatly fit into either the pediatric or adult ITP group. A deeper understanding of ITP's natural history, risk factors for chronicity, and outcomes in AYAs is a crucial first step toward developing tailored treatment algorithms. Such data could form the basis for recommendations targeting this underrepresented yet clinically distinct population. Ultimately, age-adapted trials may improve long-term outcomes, reduce toxicity, and enhance quality of life for AYAs with ITP. The AYAs collaboration-drawing on data from the Pediatric and Adult Registry on Chronic ITP (PARC-ITP), Registre Midi- Pyrénéen-France (CARMEN-France) adult registry in Toulouse, and the National Prospective Cohort for Children with Chronic Autoimmune Cytopenia (OBS'CEREVANCE) in Bordeaux, France-aims to address the information gap in AYAs with ITP. To date, four analyses have been undertaken (using data from 2004 to 2021), each addressing the major clinical aspects of ITP in patients aged 12-25 years: (1) newly diagnosed ITP, (2) chronic disease, (3) refractory courses, and (4) secondary (sITP) forms.

Adolescents and young adults (AYAs) with immune thrombocytopenia (ITP) exhibit distinct clinical features and needs, defying categorization as either adults or children. Previous findings revealed a 50% risk of chronic disease at 12 months, yet the long-term course remains unclear. This study aimed to delineate the clinical and laboratory characteristics of AYAs with chronic primary ITP. Data from patients aged 12 to 25 years with chronic disease at 1 year were extracted from 3 registries (Pediatric and Adult Registry on Chronic ITP, CEREVANCE, and Cytopénies Auto-immunes Registre Midi-Pyrénéen), covering the period from 2004 to 2021. Sustained complete remission off treatment (SCROT) occurring beyond 12 months was defined as platelet count of >100 × 109/L without treatment for at least 12 months, independently of the previous treatment strategy. A total of 427 AYAs (64% female) with chronic primary ITP were included. Clinical information was available for ∼100% of patients at initial diagnosis and at 6- and 12-month follow-ups (FUs); and for 88%, 77%, and 59% at 24, 36, and 48 months, respectively. Over time, clinical features improved gradually, with fewer patients requiring treatment. Throughout the FU period, second-line drug use increased steadily among treated patients, without affecting the need for corticosteroids and IV immunoglobulins. The proportion of new patients achieving SCROT at 24-, 36-, and 48-month FU was 10% (38/375), 9.5% (31/327), and 12% (30/250), respectively, including 23 who underwent splenectomy. AYAs achieving SCROT between 12 and 36 months displayed higher platelet counts in the first year (excluding the initial period) and received fewer IV immunoglobulin treatments beyond 12 months compared with those with ongoing disease.

Helicobacter pylori (H. pylori) infection is a continuous challenge for both gastroenterologists and pediatricians. The international guidelines regarding diagnostic and treatment pathways differ between adults and children. The pediatric guidelines are more restrictive because children are rarely affected by serious consequences, particularly in Western countries. Therefore, infected children should be treated only after a careful case-by-case evaluation by a pediatric gastroenterologist. In any case, recent studies are confirming an increasingly all-around pathological role of H. pylori even in asymptomatic children. For these reasons, following the current evidence, we feel that H. pylori-infected children could be treated starting in pre-adolescence, particularly in Eastern countries, because their stomachs have already begun to develop the biomarkers of gastric damage. Therefore, we believe that H. pylori is anyway pathogen in children. Nevertheless, the possible beneficial role of H. pylori in humans has not yet been conclusively disproved.

About one-third of all children worldwide is infected with H. pylori and its prevalence is low in developed and high in developing countries. H. pylori is mainly acquired during childhood and transmission of the bacterium commonly proceeds from person to person, especially among family members. The most frequent transmission route is from the mother to children. Various gastrointestinal and extra-gastrointestinal diseases are reported to be associated with H. pylori in children and adolescents, but the strongest recommendation for testing and treating is introduced only with children and adolescents having peptic ulcer disease. Iron deficiency anemia and chronic immune thrombocytopenic purpura are also considered for testing and treating, but the effectiveness is somewhat controversial. Invasive diagnosis is recommended, whereas none of the available diagnostic tests have 100% accuracy for reliable diagnosis, and therefore at least two or more tests should be performed. Urea breath test is the most reliable among the non-invasive tests. Because the number of antibiotics-resistant H. pylori strains is increasing, it is desirable to conduct a drug susceptibility test before treatment and to select the corresponding regime. H. pylori has been proven to be a major cause of gastric cancer and 'screen-and-treat' strategies are recommended in communities at high risk of gastric cancer. However, the application to children and adolescents is controversial. An effective vaccine is desirable, but not yet available. Screen-and-treat for adolescents has started in a few areas in Japan, where conditions are well established. New prevention strategies for gastric cancer are awaited worldwide.

There is limited information on long-term follow-up and prognostic factors for remission among children diagnosed with chronic immune thrombocytopenia (ITP). The aim of this study was to determine clinical outcomes and factors influencing remission in childhood chronic ITP.

The hospital records of children aged 0-15 years diagnosed with chronic ITP were retrospectively reviewed. Kaplan-Meier curves were fit to estimate the median time to complete remission with 95% confidence intervals (CIs). Multivariate Cox proportional hazards regression models were used to identify independent factors for remission.

A total of 113 patients were included in the analysis. The number of children achieving complete remission was 49 (46%) and the median time to remission was 7.1 years (95% CI: 4.8-11.0). The remission rates at 3, 5, 10, and 20 years were 25, 43, 60, and 75%, respectively. Factors influencing remission were platelets >60 × 10⁹ /L at the onset of chronic ITP (hazard ratio [HR]: 7.24, 95% CI: 3.0-17.5) and treatment with intravenous immunoglobulin (HR: 0.37, 95% CI: 0.16-0.84). Age, gender, and clinical factors at the time of newly diagnosed ITP including bleeding manifestations, onset of symptoms, and history of preceding infection and vaccination were not predictive of remission.

The spontaneous complete remission rates of chronic ITP were 43 and 60% at 5 and 10 years, respectively, and reached 75% at 20 years. A higher platelet level at diagnosis of chronic ITP and form of treatment were statistically significant indicators for achieving complete remission.

Primary Evans syndrome (ES) is defined by the concurrent or sequential occurrence of immune thrombocytopenia and autoimmune hemolytic anemia in the absence of an underlying etiology. The syndrome is characterized by a chronic, relapsing, and potentially fatal course requiring long-term immunosuppressive therapy. Treatment of ES is hardly evidence-based. Corticosteroids are the mainstay of therapy. Rituximab has emerged as the most widely used second-line treatment, as it can safely achieve high response rates and postpone splenectomy. An increasing number of new genetic defects involving critical pathways of immune regulation identify specific disorders, which explain cases of ES previously reported as "idiopathic".

Helicobacter pylori (H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in the last decades, abetted by modern clinical practices, may have other health consequences.

Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the human stomach for many decades without adverse consequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent abdominal pain, chronic idiopathic thrombocytopenia, and poor growth. There is evidence of the role of H. pylori in childhood iron deficiency anemia, but the results are not conclusive. The possibility of an inverse relationship between H. pylori and gastroesophageal reflux disease, as well as childhood asthma, remains a controversial question. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae.

There is paucity of data on long-term probability of remission in chronic idiopathic thrombocytopenic purpura (ITP). Aim was to study the course and factors influencing remission of chronic ITP. Chronic ITP was defined as thrombocytopenia persisting >6 months following initial diagnosis.

Case-records of children with chronic ITP, aged <14 years, were reviewed in this retrospective study (1987-2006).

Two hundred seventy children were followed. Median age at diagnosis was 6 years. Median duration of follow up was 30 months (range 6-166). Isolated thrombocytopenia (even if <10 x 10(9)/L) in the absence of "significant" bleeds, by itself was not considered an indication for drug therapy. Sixty-seven (24.8%) children attained complete remission (CR) over a median period of 18 months (range 7-120). The probabilities of remission at 5 years for males and females were 24% and 39.6%, respectively (P = 0.01). The probability of achieving remission at 10 years in children <8 and > or =8 years was 51.2% and 34%, respectively (P = 0.02). The probability of remission at 5 years for children who received some treatment, versus no treatment was 31.4% and 27%, respectively (P = 0.8). Nine of 18 children, who underwent splenectomy, achieved CR. Intracranial hemorrhage (ICH) occurred in 11 (4%) cases. The time of occurrence of ICH from onset of symptoms varied from 6 to 55 months.

The predicted spontaneous remission rate with chronic ITP was 30% and 44% at 5 and 10 years, respectively. Platelet count at diagnosis and the treatment administered did not influence remission outcomes. Age <8 years and female gender were predictors of a favorable outcome.

To investigate the effect of Helicobacter pylori eradication on platelet recovery in childhood chronic idiopathic thrombocytopenic purpura (ITP).

A multi-center randomized controlled trial was conducted. Patients aged 4-18 years, diagnosed with chronic ITP, defined by platelet count below 100 x 10(9)/L lasting more than 6 months without identified causes, were enrolled and underwent (13)C-urea breath test for diagnosis of H. pylori infection. Patients who received prednisolone more than 0.5 mg/kg per day or received other platelet-enhancing therapy were excluded. Patients with H. pylori infection were randomized into two groups: treatment and control groups. Treatment group received a standard protocol for H. pylori eradication and repeated (13)C-UBT at 4-6 weeks to confirm successful therapy while the control group received no specific treatment. Monthly platelet count was monitored for 6 months in both groups. Primary outcome was platelet recovery, defined by platelet count over 100 x 10(9)/L for at least 3 months.

Of the 55 ITP children, 16 (29.1%) had H. pylori infection. There were no differences in age, sex, duration of disease, platelet count, and the dose of prednisolone between the treatment group (n = 7) and control group (n = 9). One patient in control group was withdrawn due to massive gastrointestinal bleeding requiring a high dose prednisolone. At 6 months, platelet recovery was demonstrated in one patient in the treatment group as well as one in the control group.

No beneficial effect of H. pylori eradication on platelet recovery in childhood chronic ITP was identified.

Demographics, outcome, and management of idiopathic thrombocytopenic purpura (ITP) in children present differences between countries. Although several factors influence outcome, it is impossible to predict at diagnosis which patients will have acute or chronic disease. High rates of spontaneous remission in chronic ITP have been reported.

Data concerning 1,683 patients with ITP diagnosed from 1981 to date are presented; outcome was evaluated in 1,418 children.

Remarkable presenting features were an incidence peak in the first 2 years of age and male predominance in patients <24 months of age. Three age groups with different recovery rates (P < 0.001) were established (2-12 months: 89.8%; 1-8 years: 71.3%; 9-18 years: 49.0%). Platelet count <10 x 10(9)/L and history of previous illness were associated with higher remission rates only in patients >12 months of age. The score developed by the NOPHO Group showed a predictive value of 83.9% for acute ITP. Spontaneous remission between 6 months and 11 years from diagnosis was achieved by 107 of 325 (32.9%) non-splenectomized children with chronic ITP, and in 44.9% of them between 6 and 12 months from diagnosis.

Age and score were main prognostic factors. Infants <1 year of age are a special group with a brief course and very high recovery rate that are not influenced by other prognostic factors. Definition of groups based on age and scoring could be useful to establish differential management guidelines. The cut-off value to define chronic ITP should be changed to 12 months.

Physician attitudes regarding management of children with severe chronic immune thrombocytopenic purpura (ITP) have not been recently characterized.

We designed a survey of members of the American Society of Pediatric Hematology-Oncology (ASPHO) that described a 5-year-old female with ITP for 1 year who was unresponsive to steroids, IVIG, and anti-D immune globulin and having frequent epistaxis causing interference with her daily activities. A 13-item questionnaire evaluated physician decision-making in this setting.

Two hundred and ninety-seven surveys (35% response rate) were returned, and 295 were evaluable. Thirty-three percent of respondents stated that they would recommend splenectomy for such a child. Of those who would not recommend splenectomy, 67% reported that they would instead treat with rituximab. If initial drug therapy failed, 47% would proceed with splenectomy. Those who reported treating with rituximab initially were more likely to recommend splenectomy following failure than those who preferred other drug therapy (P < 0.0001).

Physician management of patients with chronic ITP is diverse. With the advent of new treatments such as rituximab and thrombopoetic agents it is critically important to compare their cost, adverse effects and efficacy with splenectomy in order to optimally guide treatment practices.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low circulating platelet count caused by destruction of antibody-sensitized platelets in the reticuloendothelial system. ITP can be classified as childhood versus adult, acute versus chronic, and primary versus secondary. Persistence of thrombocytopenia defines the chronic form of the disorder. Secondary causes of ITP include collagen vascular disorders, immune deficiencies, and some chronic infections. This review focuses on the diagnosis and management of children who have acute and chronic ITP. Emphasis is placed on areas of controversy and new therapies.

Chronic ITP rarely presents with severe bleeding episodes (SBE). Number and duration of SBE were evaluated in relation to the cost of management. Out of 157 chronic ITP patients attending our institution from 1994 to 2003, 37 patients, <16 years with persistent thrombocytopenia (>6 months), suffering from SBE or platelet count<10x10(9)/L were prospectively randomized to receive either intravenous immunoglobulins (IVIG), anti-D immunoglobulin (anti-D) or high-dose methyl prednisolone (HDMP). Sixty-one patient-years were followed, during which 351 SBE were documented. The high-cost management (IVIG and anti-D) showed insignificantly better platelet recovery, less frequent SBE with shorter duration per patient, higher rate of CR, and less splenectomy in contrast to the steroid groups. The effectiveness of high-cost management compared with methyl prednisolone could not be documented in this study.

Two hundred thirty of 696 evaluable children were identified as having chronic idiopathic thrombocytopenic purpura (ITP). Splenectomy was performed in 30 (13%), achieving remission in 22 (73%). Favorable response was associated to higher initial platelet count. Spontaneous remission was achieved by 53/200 non-splenectomized patients (26.5%), up to 10 years from diagnosis. More than half of them recovered between 6th and 12th month from diagnosis. The recovery rate was significantly higher (P=0.03) in children aged<9 years (31.2%) than in older children (14.6%). No reliable factor predictive of response in individual cases is still available.

Approximately 5% of chronic immune thrombocytopenic purpura (ITP) manifests itself as symptomatic, severe thrombocytopenia requiring splenectomy. The surgical procedure increases the risk of serious hemorrhage, especially in patients refractory to platelet transfusions. Recombinant factor VIIa (rFVIIa) has been found to enhance thrombin generation on activated platelets and may be a promising agent in preventing life-threatening bleedings. The administration of rFVIIa in two patients with severe refractory ITP, who underwent splenectomy, is presented. Combined therapy with agents of different mechanisms of action could be useful in cases with the highest probability of bleeding.

Idiopathic thrombocytopenic purpura (ITP) is a hematologic disorder characterized by the destruction of antibody-coated platelets in the reticuloendothelial system. Whereas 70% to 80% of children experience the acute form of the disease and recover within a few weeks or months after diagnosis, most adults have persistent disease and will require therapy. Principles of management are largely predicated on the extent of thrombocytopenia and symptoms of disease. Minimizing the toxicity associated with treatment while achieving hemostatic platelet counts are essential goals of treatment. Although there are numerous therapeutic options, neither consensus among experts nor clear algorithms to treat this complex disease exist. This article will review appropriate treatment options available for adult patients with ITP prior to splenectomy, at splenectomy, and following splenectomy. In addition to conventional agents such as corticosteroids and intravenous immune globulin (IVIg), the role of newer therapies with diverse mechanisms of action, such as rituximab, anti-D, and thrombopoietin (TPO)-like agents, will be highlighted. When used as either monotherapy or in combination with conventional therapeutics, these treatments may offer a more tolerable side effect profile and improved clinical benefit compared to existing drugs.

The management of chronic and refractory idiopathic thrombocytopenic purpura (ITP) in children is controversial. We conducted a retrospective review of our single center experience in China between 1990 and 2003 with splenectomy for chronic ITP in children in order to determine the initial and long-term hematological response, morbidity, mortality, predictors of response to splenectomy and the therapy in children who failed splenectomy. Of 65 children analyzed, the overall immediate clinical response to splenectomy was 89.2%. The median postsplenectomy follow-up time was 52 months (8-124). During follow-up, 9 children (13.8%) relapsed within a median time of 6 months (2-58). The overall morbidity was 1.5% and perioperative mortality was zero. During follow-up, 1 child died of intracranial hemorrhage (ICH) and 1 died of overwhelming postsplenectomy infection (OPSI). The platelet count at day 7 after splenectomy was a predictor of a sustained response to splenectomy but no preoperative parameters were predictors of the response to splenectomy. Of the 15 children who failed splenectomy, excluding the one who died of ICH, only 2 children intermittently required corticosteroids and IVIG. Splenectomy is a potential therapy to provide long-term control of disease in children with chronic ITP and is associated with low morbidity and mortality. The risk of fulminant sepsis remains an omnipresent concern. Antipneumococcal vaccination and antibiotic prophylaxis should be recommended and children should receive timely and adequate antibiotics for bacteria infection to lessen the problem of OPSI.

Patients having immune cytopenias produce antibodies that target hematopoietic cells resulting in their phagocytosis and intracellular destruction. Early reports suggested that phagocytosis could be inhibited by interfering with membrane thiol (SH) groups on phagocytes. Thus, whether chemical compounds that interact with SH or disulfide (SS) groups on mononuclear phagocytes can inhibit phagocytosis of antibody-coated cells was examined.

A monocyte monolayer assay (MMA), which examines the in vitro monocyte-macrophage (Mphi) interaction with anti-Rh(D)-coated red cells (RBCs), was used to study the ability of different SH and SS chemicals to inhibit the Fc receptor-mediated phagocytosis of sensitized RBCs. The compounds examined included thimerosal, dithiothreitol (DTT), pentane-1-thiol, and two recently described SH and two SS chemicals that have been synthesized.

All compounds were found to be able to inhibit phagocytosis to varying degrees correlating to the structure of the molecule. In general, those compounds that interact with free SH groups to inhibit phagocytosis were found better than SH-containing compounds that interact with SSs. Thimerosal and p-nitrophenyl methyl disulfide were the most effective compounds inhibiting phagocytosis. Both chemicals showed greater than 50 percent inhibition at concentrations as low as 10(-9) mol per L. DTT was the least effective compound tested. Only thimerosal showed significant toxicity, as determined by decreased cell viability and increased apoptosis, but only at concentrations of 10(-8) mol per L. The effect of chemical treatment was on attachment rather than on phagocytosis itself. Fcgamma receptor-independent endocytosis was not affected by the chemical treatment.

These studies indicate that pharmacologic strategies that target SH groups on mononuclear phagocytes may have future efficacy for the treatment of immune cytopenias.

About 25-30% of children with acute idiopathic thrombocytopenia (ITP) develop chronic disease. It is not well known which patient characteristics influence the course of the ITP. A prospective study in 60 children with newly diagnosed ITP was performed. The aim of the study was to identify patient characteristics at the onset of thrombocytopenia that predicts the progression to chronic ITP. Clinical data and blood samples were collected at several time points during the first 6 months of the disease. Variables predicting chronic disease, as calculated in a multivariate logistic regression analysis, were a platelet count >10 x 10(9)/l at the onset [odds ratio (OR) 1.1, 95% confidence interval (CI) 1.01-1.14], the absence of infection shortly before the onset of the disease (OR 4.8, CI 1.16-19.57) and FGR2B-232I/T genotype (OR 7.9, CI 0.96-65.27). The latter may point at an immune-modulating role of Fc gamma RIIb in ITP. Although only three patients had serious bleeds, 35 patients received immune-modulating treatment for low platelet counts only. Seventeen patients were treated with intravenous immunoglobulin (IVIG) and 18 patients received corticosteroids. Patient variables did not differ between these treatment groups. However, patients receiving IVIG had significantly lower risk for chronic disease.