Childhood immune thrombocytopenic purpura: diagnosis and management

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.     

Effects of COVID-19 vaccination on platelet counts and bleeding in children,adolescents, and young adults with immune thrombocytopenia

Coronavirus disease 2019 (COVID-19) vaccines rarely cause de novo immune thrombocytopenia (ITP) but may worsen preexisting ITP in adults. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines impact platelet counts and bleeding in children, adolescents, and young adults (C-AYA) with preexisting ITP is unknown. We report here the very limited effect of COVID-19 vaccination on platelet counts and bleeding in a single-center series of 2 C-AYA with ITP. No patient experienced worsening bleeding and only one child had a significant decrease in platelet count which improved spontaneously to her baseline without intervention. SARS-CoV2 vaccination was safe in C-AYA with ITP in this small cohort.     

Mechanisms in childhood idiopathic thrombocytopenic purpura (ITP)

The concepts of the pathological mechanisms in childhood idiopathic thrombocytopenic purpura (ITP) have, to a great extent, been based on clinical experience and on data generated in adults. Studies performed in children have demonstrated that platelet antigen-specific autoantibodies are present in chronic ITP and, to a lesser extent, in acute ITP. It is, however, likely that the mechanisms initiating the production of autoantibodies are different in the two entities. In acute ITP, production of autoantibodies and immune complexes is probably linked to a transient antiviral immune response. Chronic ITP in children is an autoimmune process which eventually is reversible in many cases. The initiating factors, as in other autoimmune disorders, are yet to be elucidated.     

Platelet-associated immunoglobulin G in childhood idiopathic thrombocytopenic purpura

Platelet-associated IgG was studied in children with acute and chronic ITP and in patients with thrombocytopenic SLE, using the microtiter solid-phase radioimmunoassay. Of the children with acute ITP, 85% had elevated PAIgG levels. The degree of elevation of PAIgG at onset of disease did not correlate with the development of chronicity. Of the children with acute ITP, clinically and hematologically indistinguishable from the rest, 15% had normal PAIgG values. All of 22 children with chronic ITP had elevated PAIgG values. Although there was good correlation between the platelet count and the PAIgG value in children with chronic ITP, the association was not as striking in those with acute ITP; thus, factors in addition to the level of PAIgG may contribute to the thrombocytopenia in the latter group. Patients with SLE and thrombocytopenia had higher values of PAIgG than would be predicted from the platelet count; the PAIgG value is probably not the only factor determining the degree of immune thrombocytopenia.     

Evaluation of a simple immunodiffusion technique for quantitation of platelet-associated immunoglobulin G in childhood immune thrombocytopenias

Platelet-associated IgG (PAIgG) was quantitated in 33 children with immune thrombocytopenia and platelet counts less than 100 X 10(9)/liter using a simple radial immunodiffusion (RID) assay. Elevated PAIgG levels were found in 76% (16/21) of children with acute idiopathic thrombocytopenic purpura (ITP), 88% (7/8) of children with chronic ITP, and all four children studied with systemic lupus erythematosus and thrombocytopenia. Normal PAIgG values were found in children with the following disorders: malignancy and chemotherapy-related thrombocytopenia; ITP in remission (platelet counts greater than 150 X 10(9)/liter); various nonimmune hematologic disorders and juvenile rheumatoid arthritis, these children having normal platelet counts. In children with acute ITP, elevated PAIgG values at initial presentation fell to within the normal range when clinical remission occurred. The RID assay can be easily established in most hematology laboratories and has the advantage that solubilized "test" platelets used in the assay can be stored frozen prior to analysis. We conclude that this simple technique is of value in the evaluation of childhood thrombocytopenic states and yields results comparable to those reported using more complex antiplatelet antibody assays.     

Complete platelet recovery after treatment of Helicobacter pylori infection in a child with chronic immune thrombocytopenic purpura: a case report

Helicobacter pylori gastritis has been associated with autoimmune disease, including immune thrombocytopenic purpura (ITP). The most recent reports also have supported this association in adults. ITP in children differs from that in adults in terms of clinical picture and mechanisms of thrombocytopenia. The authors report a case of a 12-year-old boy with chronic ITP, in whom they detected H. pylori infection and observed a complete platelet recovery after the eradication of H. pylori.     

High-Dose Intravenous Immunoglobulin as Single Therapy in a Child with Autoimmune Hemolytic Anemia

Between 1975 and 1992 450 children with idiopathic thrombocytopenic purpura (ITP) were diagnosed, and of those 100 (22%) developed the chronic form of the disease. Approximately half the patients with chronic ITP presented with mild to moderate hemorrhagic manifestations at the onset of purpura (30 cases) andlor later during the course of the disease (25 cases). The incidence of intracranial hemorrhage was 1 %, and the mortality rate due to overwhelming septicemia after splenectomy was also 1%. Overall one-third of the patients received no therapy; two-thirds of them went into spontaneous remission within 8 months to 8 years from the onset of ITP. Steroids given in conventional or high doses (51 cases) achieved a transient (if any) rise in platelet count, but in no case were steroids curative. Remission related to intravenous immune globulin (IVIG) therapy was noticed in 38.5% of the children (10 of 26) after variable courses. The response rate to splenectomy was 95.0%. Ultimately the long-term outcome in children with chronic ITP was as follows: remission, 58 cases (spontaneous, 30; after IVIG therapy, 10; after splenectomy, 18); hemostatic platelet values, 22 cases (spontaneous, 16; after IVIG, 5; after splenectomy, I). Thirteen children were lost in follow-up, and 7 remain thrombocytopenic but asymptomatic. These data indicate that chronic ITP in childhood runs a benign course in most cases and may remit with or without therapy euen several years from onset. Therefore, therapeutic intervention has to be individvalized, and splenectomy, which is not always safe, should be reserved for problematic cases that fail to respond to conventional therapeutic modalities.     

儿童免疫性血小板减少症发病机制研究进展

免疫性血小板减少症(immune thrombocytopenia,ITP)是一种由自身免疫介导的出血性疾病,其特点为血小板破坏增多和生成不足.ITP发病机制复杂多样,具有异质性,至今尚未完全明确,在儿童中尤其突出.现有研究表明,免疫失耐受引起各种免疫细胞或分子异常,进而导致血小板破坏增多或生成不足,是ITP的核心发病...     

COMPLETE PLATELET RECOVERY AFTER TREATMENT OF HELICOBACTER PYLORI INFECTION IN A CHILD WITH CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA: A Case Report

Helicobacter pylori gastritis has been associated with autoimmune disease, including immune thrombocytopenic purpura (ITP). The most recent reports also have supported this association in adults. ITP in children differs from that in adults in terms of clinical picture and mechanisms of thrombocytopenia. The authors report a case of a 12-year-old boy with chronic ITP, in whom they detected H. pylori infection and observed a complete platelet recovery after the eradication of H. pylori.     

Idiopathic thrombocytopenic purpura in children. The case for management without corticosteroids

Acute ITP in children under 13 years of age is generally a benign, self-limited condition with spontaneous recovery occurring within a matter of days or weeks. Our analysis of platelet data indicate no advantage in terms of rate of recovery when steroids are used. In fact, the median of 3 weeks and mean of 3 1/2 weeks from onset to recovery in the nonsteroid-treated children were significantly better than the corresponding figures in the steroid-treated group. In addition, while reducing the risk of intracranial hemorrhage is generally given as the chief therapeutic rationale for using steroids, we have not seen a single case of ICH among 465 consecutive cases of acute ITP in children, the majority (93%) of whom did not receive steroids. On the other hand, adolescents, as adults, with ITP often have the autoimmune (chronic) form of the disease. In this group, corticosteroids may be of at least transient benefit and should be used.     

Platelet-Associated IgG in Children - Values and Evaluation of PAIgG in Various Thrombocytopenias -

Platelet-associated IgG (PAIgG) levels were measured in 60 children with ITP (46-chronic, 14-acute) using Fab-anti Fab radioimmunoassay method described by McMillan et al. In some patients platelet binding IgG in serum (PBIgG) was also determined at the same time. Patients with ITP had significantly greater PAIgG levels than 30 normal subjects and 13 non-immune thrombocytopenic controls. Elevated PAIgG values did not correlate with parameters of platelet size (mean platelet volume; MPV and percentage of large platelet; PLP) and so these data indicated that high levels of PAIgG in ITP were not due to nonspecific adhesion of serum IgG to megathrombocytes usually increased in this disorder, but due to specific immunological reaction. PBIgG IgG values were also elevated in patients with pretreated chronic ITP, but high levels remained even after successful splenectomy. Furthermore, serial determination of PAIgG values were obtained in some patients with chronic ITP who underwent splenectomy and with acute ITP who achieved spontaneous remission. PAIgG returned to normal levels when thrombocytopenia disappeared. PAIgG seems to be the most reproducible indicator which reflects transition of the clinical picture in this disorder.     

Prednisone treatment of acute idiopathic thrombocytopenic purpura of childhood. Advantages

Idiopathic thrombocytopenic purpura (ITP), an acquired hemorrhagic disorder, is characterized by the abrupt onset of thrombocytopenia despite normal megakaryocytic productivity. An accumulating body of evidence, including the recent demonstration of elevated levels of platelet-associated IgG, points to an immune etiology of acute childhood ITP. Although spontaneous recovery occurs in 80-90% of patients within 4 months of diagnosis, hemorrhagic complications may occur. Considerable evidence exists which suggests the efficacy of corticosteroid use in this disorder. Several clinical studies have shown that steroids may shorten the time to platelet count recovery, thus reducing the time at risk for hemorrhagic complications. The authors conclude with treatment recommendations for childhood ITP which include a brief course of prednisone.     

The role of Helicobacter pylori infection in children with acute immune thrombocytopenic purpura

The outcome of immune thrombocytopenic purpura (ITP) is classified as acute or chronic depending on whether platelet count returns to normal. The prevalence of Helicobacter pylori infection increases with age and is independent of gender. We investigated the prevalence of H. pylori infection in Chinese children from Northern Taiwan and analyzed the association between H. pylori infection and acute ITP. Our prospective cohort studies found no statistically significant relation between H. pylori infection and acute ITP. There is therefore no indication to screen children with presumed acute ITP for H. pylori infection.     

原发性免疫性血小板减少症儿童生活质量及其影响因素研究进展

原发性免疫性血小板减少症(primary immune thrombocytopenia,ITP)是儿童最常见的出血性疾病,常表现为皮肤和黏膜出血,罕见颅内出血。儿童ITP为急性自限性疾病,大多数出血倾向重但预后良好;少数迁延反复,呈慢性趋势。尽管儿童ITP严重出血风险低,但慢性ITP血小板计数反复减少常引起家属的担忧,故患儿的日常活动常会受到限制。此外,治疗药物引起的相关不良反应、对病程迁延及疾病预后的担忧等都会影响到患儿的健康及相关生活质量。该文主要针对ITP儿童的生活质量及主要影响因素研究进展展开论述。     

Idiopathic thrombocytopenic purpura: beyond consensus

Idiopathic thrombocytopenic purpura (ITP) is the most common acquired bleeding disorder encountered by pediatricians. Most children with ITP have minimal bleeding and complete platelet count recovery within weeks to months. Therapy for ITP has ranged from close observation without medical intervention to aggressive management with corticosteroids, intravenous immunoglobulin G, or anti-D immune globulin. The topic of ITP has incited great debate among practitioners, and this debate prompted the development of ITP practice guidelines by the British Paediatric Haematology Group in 1992 and by the American Society of Hematology in 1996. A better understanding of the clinical course of, risk for significant bleeding in, and optimal evaluation and therapy of childhood ITP will require carefully designed, multicenter, clinical trials.     

In vitro megakaryocytopoiesis in children with acute idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) of childhood is a disorder characterized by a history of previous viral illness followed by acute onset of low circulating platelet count with present or increased megakaryocytes in the bone marrow. The majority of children recover a normal platelet count within 6 months to 1 year after onset of the disease. To better understand the regulation of megakaryocytopoiesis in this disorder, we studied nine patients with childhood ITP with the plasma clot colony assay in vitro for megakaryocyte colony forming units (CFU-Mk). Mononuclear bone marrow cells from some of the patients with ITP contained greater numbers of CFU-Mk and greater numbers of cells per colony than mononuclear bone marrow cells from healthy adult volunteers (p less than 0.026) when the cultures contained no added megakaryocyte colony-stimulating activity (Mk-CSA). The serum from patients with ITP did not stimulate in vitro megakaryocytopoiesis from healthy adult volunteers' bone marrow mononuclear cells above baseline values. These findings are consistent with the hypothesis that a decrease in bone marrow megakaryocytes is needed for Mk-CSA production. Alternatively, Mk-CSA is consumed by active megakaryocytopoiesis in the bone marrow.     

Post‐varicella thrombocytopenic purpura

Aims: 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. Methods: 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. Results: 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. Conclusions: 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.     

Ethnicity and environment may affect the phenotype of immune thrombocytopenic purpura in children

Little is known about the influence of environmental and ethnic factors on the epidemiology of immune thrombocytopenic purpura (ITP). Therefore we compared the initial presentation and condition after 6 mo in 90 Vietnamese and 89 German and Swiss children with newly diagnosed ITP. Data from the two cohorts were collected within the same time period. No differences in age and sex were observed between the Asian and European cohorts, but significant differences between initial platelet count, the occurrence of dry versus wet bleeding symptoms, and infection preceding the onset of ITP were found. Children who had chronic ITP also differed with respect to platelet count and postinfectious state, but not initial bleeding type. In addition, chronic ITP occurred more often than expected with a male to female ratio of 1.2 in Vietnam and 2 in Germany and Switzerland. The data support the potential influence of environmental or ethnic factors on the different aspects of ITP, and point to the need for further epidemiologic investigations.     

Evaluation and treatment of thrombocytopenia in the neonatal intensive care unit

Phlebotomy-induced anaemia excepted, thrombocytopenia is the most common haematological abnormality in neonatal intensive care unit (NICU) patients. Roughly one-quarter of all NICU patients and half of all sick preterm neonates develop thrombocytopenia. Whereas a large number of varied precipitating conditions has been identified, early-onset thrombocytopenia (<72 h) is most commonly associated with fetomaternal conditions complicated by placental insufficiency and/or fetal hypoxia, e.g. maternal pre-eclampsia and fetal intrauterine growth restriction. The resulting neonatal thrombocytopenia is usually mild to moderate, resolves spontaneously and requires no specific therapy. Deviation from this pattern of thrombocytopenia suggests the presence of more significant precipitating conditions. The most important of these are the immune thrombocytopenias, and every NICU should develop investigation and treatment protocols to manage these cases promptly and avoid unnecessary risk of haemorrhage. In contrast, late-onset thrombocytopenia (>72 h) is almost always associated with sepsis or necrotizing enterocolitis and the associated thrombocytopenia is severe, prolonged and often requires treatment by platelet transfusion. Unfortunately, evidence-based guidelines for platelet transfusion therapy in NICU patients are currently unavailable, making it difficult to define widely accepted thresholds for transfusion and leading to a significant variation in transfusion practice between centres. CONCLUSION: While improving this situation remains a pressing need, the growing evidence that impaired megakaryocytopoiesis and platelet production are major contributors to many neonatal thrombocytopenias suggests that recombinant haemopoietic growth factors, including thrombopoietin and interleukin-11, may be useful future therapies to ameliorate neonatal thrombocytopenia.     

Platelet-associated immunoglobulin G in childhood idiopathic thrombocytopenic purpura

Childhood ITP is an acquired hemorrhagic disorder with a heterogeneous clinical course. We measured PAIgG levels in 20 children with ITP (7 acute, 13 chronic). Both groups had significantly greater PAIgG values than age-matched normal subjects and thrombocytopenic controls (P less than 0.001). In addition, PAIgG values in chronic ITP were significantly lower than those in acute ITP (P less than 0.003). Serial PAIgG values were obtained in some patients; most returned to normal in association with clinical recovery. The measurement of PAIgG is useful in the diagnosis and follow-up of childhood ITP. PAIgG values may assist in differentiating acute and chronic disease in children.