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.     

Peritoneal hemorrhage due to a ruptured ovarian cyst in ITP

Immune thrombocytopenic purpura in children rarely causes severe bleeding. The incidence of intracranial hemorrhage is approximately 0.2% to 1.0%, and severe bleeding (defined as persistent epistaxis, melena, menorrhagia, gastrointestinal bleeding, etc, requiring hospitalization or transfusion) occurs in only 5% of patients. Epstein-Barr virus (EBV) associated idiopathic thrombocytopenic purpura (ITP) tends to behave similarly to non-EBV - associated ITP with no increase in hemorrhagic complications and only a small increase in time to remission. Immune thrombocytopenic purpura diagnosed in adolescence is more likely to be chronic then in childhood ITP, but has a higher rate of spontaneous resolution than in adults. However, females in this age group are in their early childbearing years and present a unique set of possible hemorrhagic complications not seen in younger patients. We present the case of an 18-year-old female with EBV-associated ITP, who developed a severe intra-abdominal bleed secondary to a hemorrhagic ovarian cyst.     

Idiopathic thrombocytopenic purpura in adults

Immune thrombocytopenic purpura (ITP) is an organ-specific autoimmune disorder in which platelets opsonized by antiplatelet antibodies are destroyed by the reticuloendothelial system. As a result the peripheral blood platelet count is low; if sufficiently severe, it may lead to bruising and mucocutaneous bleeding. The disorder may occur in adults and in children; in the former the disease affects primarily females, whereas the childhood type affects the sexes equally. For most individuals the disorder is minor, requiring little treatment, but patients with more severe forms of the disease require therapy to elevate the platelet count to a safe level to prevent serious bleeding. Therapies include corticosteroids, intravenous immunoglobulin, splenectomy, and immunosuppressive agents. Because there have been few trials in ITP, there is little evidence to guide treatment, and all the treatments may have adverse effects in terms of morbidity and mortality. The American Society of Hematology and British Committee for Standards in Haematology guidelines provide a framework for management but nonetheless are based on little evidence. In this paper the authors review the management of ITP in adults, children, and pregnant women and highlight some of the novel therapies being explored in this disorder, in addition to some of the ongoing laboratory research exploring the mechanisms underlying the disease.     

Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS)

BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response.     

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.     

Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms. Mean age at diagnosis and duration of follow-up were similar for both groups. Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a 125I-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.     

儿童难治性特发性血小板减少性紫癜的治疗进展

特发性血小板减少性紫癜(ITP)是一种自身免疫性疾病,是临床最常见的出血性疾病.治疗以糖皮质激素、免疫抑制剂、脾切除等非特异性手段为主,但副反应明显,且约1/3的患儿治疗无效,成为难治性ITP.儿童难治性ITP目前尚无特效根治约物及方法,治疗应个体化,治疗选择应根据血小板计数和出血状态而定.近年对ITP自身免疫发病机制的深入研究令许多新的定向免疫干预措施开始进入临床研究阶段,实施定向免疫干预将是今后ITP诊疗的方向.文章结合ITP的发病机制对这些进展作一概述.     

Evaluation of clinical characteristics, diagnosis and management in childhood immune thrombocytopenic purpura: a single center's experience

Diagnostic evaluation and management in childhood immune thrombocytopenic purpura (ITP) are controversial. We reviewed the files of 162 children with ITP to evaluate clinical characteristics, response to treatment and outcome. History of antecedent infection, vaccination and serologic evidence for acute viral infection were present in 48%, 5% and 17% of the patients, respectively. At diagnosis, two-thirds of the patients had a platelet count of <10,000/microl but only 10% had major bleedings. Intracranial hemorrhage was seen in two patients (1.2%) with a mortality rate of 0.6%. Sixteen percent developed chronic ITP. The rate of platelet recovery with mega-dose methylprednisolone (30 mg/kg/d for 3 and 20 mg/kg/d for 4 days) was similar to that obtained with intravenous immunoglobulin or oral prednisolone. Four of seven patients with ITP responded to splenectomy. These data show that mode of treatment has no effect on the clinical course and prognosis of childhood ITP.     

脾切除治疗儿童慢性特发性血小板减少性紫癜的Meta分析

目的从循证医学的角度来探讨脾切除治疗儿童特发性血小板减少性紫癜（ITP）的临床疗效。方法检索中国期刊网、万方数据库、中国生物医学文献数据库及Pubmed，获得已发表的脾切除治疗儿童ITP的相关文献。根据临床和统计标准进行合并分析，评价脾切除治疗儿童ITP的效果。结果共检索到符合条件的文献6篇，并纳入Meta分析。共行脾切除224例，所有患儿脾切除年龄均大于5岁，从诊断到脾切除的时间大于6个月。利用Revman4．2软件对所有文献的有效率进行Meta分析。结果显示Z值为1．51，P〉0．05，总体OR为2．17（95％CI，0．79～5．95）。结论 对于儿童慢性ITP，因脾切除可以取得与内科治疗基本相等的疗效，因此，对内科治疗失败，年龄大于5岁，病程大于6个月者，可考虑行脾切除术，但应严格遵照手术指征操作。     

The effects of megadose methylprednisolone therapy on the immune system in childhood immune thrombocytopenia

Immune thrombocytopenia (ITP) is a frequently encountered disease in childhood. Recent reports pointed to the benefit of high-dose steroid in ITP treatment since it resulted in a better outcome in a shorter time than IV immunoglobulin therapy. In the authors' clinic, mainly after 1984, megadose methyl prednisolone (MDMP) has been used for ITP treatment. There is no report that includes an extensive immune system examination of megadose steroid effect in childhood ITP. The purpose of this study is to determine the effects of MDMP therapy on the immune system in childhood ITP for serum immunoglobulins, absolute lymphocyte and lymphocyte subclass counts, and in vitro blastogenic responses to mitogens. The authors have demonstrated that lymphocyte subtypes (CD3, CD4, CD8, CD19) and serum immunoglobulin G, A, M increased after a short-course MDMP therapy in comparison to pretreatment values in mixed group (acute + chronic) of childhood ITP patients. Also blastic transformation function of lymphocytes with Conca-A and phytohemaglutinin showed an upward trend in 6 of the 9 patients. Steroid are thought to have a suppressive effect on the immune system but this study suggests that short-course MDMP may not be hazardous to the immune system.     

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.     

Kaposiformes kongenitales Hämangioendotheliom als Geburtshindernis und postpartaler Notfall

Kaposiform hemangioendothelioma (KHE) is a rare, weakly malignant vascular tumor that occurs nearly exclusively during infancy and childhood. It is often complicated by the Kasabach-Merritt phenomenon (KMP), severe thrombocytopenia and consumptive coagulopathy which can lead to severe hemorrhagic complications. This article describes the case of a term newborn with a protracted birth caused by a fulminant swollen, red-colored right arm and a threatening circulation disorder of the ipsilateral hand. The clinical, radiological and laboratory findings including histological analysis were in line with the diagnosis of congenital KHE with KMP. High-dose administration of prednisolone, acetylsalicylic acid and later sirolimus therapy resulted in a clear reduction of the tumor mass and recovery from thrombocytopenia. During the time of treatment the tumor became steroid-dependent and in the further course also vincristine-dependent; therefore, laser therapy was initiated, which successfully caused the tumor to disappear. Additional treatment with propranolol showed no positive effects. Neonatal KHE can present as an emergency and as in this case requires immediate treatment due to thrombocytopenia and imminent loss of hand function from circulation failure.     

Idiopathische thrombozytopenische Purpura im Kindesalter

Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder characterised by shortened platelet survival. ITP is heterogeneous and is affected by endogenous and acquired factors. The diagnosis is one of exclusion, meaning that differential diagnosis is always important. Because of the unknown aetiology and the lack of clinical data collected from controlled prospective studies, the diagnosis and management of patients with ITP are controversial. The objective in prospective trials has been to alter the velocity of platelet increase. This study goal is frequently extrapolated to clinical situations, but no evidence has been found to show that a fast increase in the platelet count is clinically significant. The treatment of a patient with ITP is generally directed at preventing life-threatening haemorrhages, which are very rare in childhood. The goals of management and the study end-points in clinical trials should be re-evaluated. Important aspects are bleeding, quality of life for the patient and adherents, side effects of drugs and economic matters.     

Idiopathic thrombocytopenic purpura of childhood

Idiopathic thrombocytopenic purpura (ITP) is a benign hemorrhagic disorder characterised by peripheral thrombocytopenia and increased megakaryocytes in the bone marrow. The exact pathogenesis of ITP is not well understood. The adherence of viral induced immune complexes to the platelet membrane is thought to trigger the phagocytosis of damaged platelets by macrophages in the reticuloendothelial system. The role of platelet associated IgG in the pathogenesis of ITP is under investigation. Although spontaneous recovery is observed in 80–90% of patients, a short course of steroid therapy is recommended to reduce the duration of thrombocytopenia. The steroids however, have no influence on the course or outcome of the disease, and their possible role in reducing the incidence of intracranial hemorrhage (ICH) is unknown. Emergency management of patients presenting with signs and symptoms suggestive of ICH is essential to prevent the fatal outcome. Approximately 10–20% of patients develop chronic ITP. Splenectomy, considered the treatment of choice in these patients, is not always curative. The post-splenectomy sepsis also imposes a great risk for these individuals. Recent experience with intravenous immunoglobulin (IV IgG) treatment indicates that the splenectomy could safely be deferred, or even avoided in chronic ITP. The use of IV IgG in acute ITP is being investigated.     

Interferon-alpha therapy in idiopathic thrombocytopenic purpura

BACKGROUND: Acute idiopathic thrombocytopenic purpura (ITP) represents the most frequent hemorrhagic diathesis in childhood. Up to 30% of patients with ITP are regarded as refractory to standard therapy. The rare mortality from acute ITP in childhood is almost exclusively due to intracranial hemorrhage. This complication occurs in less than 1% of ITP patients. This study was designed to evaluate the effect of alpha-interferon (IFN-alpha) in eight patients whom did not respond to conventional therapy. METHOD: In spite of conventional therapies, the patient whose platelet count could not be increased to 50;10(9)/L were accepted as refractory ITP. Eight of these patients whose platelet count lower than 20;10(9)/L were included in the prospective cohort study. Interferon alpha 2b 5 MU/m(2) was administered subcutaneously three times a week, totalling 12 times in a month. According to the platelet count on the 28th day of therapy, we grouped the patients into three categories. After 60 days, the survey was re-evaluated according to the platelet count. RESULTS: The mean age of children was 3.5+/-2.5 (ranged between 3.5 and 9) years. Six of them were boys and two were girls. There was no response in one patient, partial response in one, and good response in six patients on the 28th day of therapy. The maximum rise in platelet count was observed from 7 to 14 days after the initiation of interferon. The median platelet count which was 15+/-5;10(9)/L before therapy, raised to 60+/-12;10(9)/L after therapy. However, on the 60th day of therapy, there were only two patients who had a platelet count over 100;10(9)/L. CONCLUSION: In our study, we did not observe the long-term benefit of IFN-alpha therapy in refractor ITP in childhood. However, in good responding patients, platelet levels were increased in a short time. Alpha-interferon may be alternative therapy for patients whom had a platelet count below 20;10(9)/L and not responding to standard therapy, or for patients whom immunosuppressive therapy is contraindicated.     

Immune thrombocytopenia following successful treatment of cancer in children

A predisposition to developing immune thrombocytopenia (ITP) has not been reported in survivors of childhood cancer. We report a case series of childhood cancer survivors who developed an isolated thrombocytopenia in the presence of a normocellular bone marrow. Five children, two with endodermal sinus tumors and three with acute lymphoblastic leukemia, developed ITP at a median of 4 years (range: 0.2-8 years) after completion of therapy. We suggest the association of ITP in survivors of childhood malignancy may not be co-incidental as chemotherapy may cause persistent immune dysfunction.     

Immune Thrombocytopenia in Children: Consensus and Controversies

Indian Journal of Pediatrics - Newly diagnosed immune thrombocytopenia (ITP) is a relatively common disorder of childhood that does not require an exhaustive laboratory workup for diagnosis. A...     

Local and cultural aspects of childhood idiopathic thrombocytopenic purpura: a summary of statements from the 12 countries worldwide

Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous bleeding disorder. The Intercontinental Childhood ITP Study Group (ICIS) analyzed demographic data and outcome in a prospective registry of over 2,000 children with ITP. In addition, participating centers from 12 different countries worldwide were asked to describe their local and cultural aspects of ITP management to provide a summary statement of the variable diagnostic and management approaches for childhood ITP. The statements of the 15 reports from 12 countries are summarized under eight main areas to reflect the variability in approach to ITP among different countries. The management of ITP in children differs dramatically worldwide in terms of observation only, medical treatment, bleeding symptoms, acceptable platelet counts, need for hospitalization or outpatient treatment, and medical care climate. The majority of experimental treatments, surveys, and guidelines are not evidence-based. Although there is a great need for cooperative studies to learn more about diagnosis, management, and prognosis in the heterogeneous disorder of ITP, local and cultural variations must be considered in international investigations.     

Familial study of factor XI deficiency. Presurgical prophylactic treatment with desmopressin plus antifibrinolytics

Factor XI deficiency is a rare inherited coagulation disorder. It rarely produces spontaneous bleeding although patients with this disorder are at risk for hemorrhagic complications after trauma or surgery. Because there is no clear correlation between the tendency to bleed and the severity of the disease itself, predicting hemorrhagic complications after surgery in patients with mild disease is difficult. This hereditary deficiency is characterized by prolongation of activated partial thromboplastin time with normal prothrombin time, and the demonstration of selective plasma factor XI deficit. Currently available products in the therapeutic arsenal are transfusion of fresh-frozen plasma, virus-inactivated factor XI concentrates, desmopressin (DDAVP) and antifibrinolytic drugs, whether alone or in combination. We describe a family with two affected children, in which the deficiency was identified as an autosomal recessive trait. Of the two patients, one required prophylactic treatment with desmopressin and tranexamic acid before surgery; the treatment was successful and no related complications were observed. The long-term outcome of individuals with this disease seems to be good with continuous follow up and early control of hemorrhagic episodes. Prophylactic therapy is not required, except when surgery is anticipated.     

人微小病毒B19感染与儿童特发性血小板减少性紫癜关系的meta分析

目的：综合分析人微小病毒B19感染与儿童特发性血小板减少性紫癜( ITP)的关系。方法：计算机检索中国期刊全文数据库、万方数据库, 检索时间从1994~2008年,纳入人微小病毒B19感染与儿童ITP关系的病例对照研究,对文献数据进行meta分析。结果：共纳入8个研究,其中病例组516例,对照组246例。meta分析显示人微小病毒B19感染在病例组的表达高于对照组（OR=13.71,95%CI=7.07～26.59,Z=7.75, P<0.01）。结论：人微小病毒B19感染与儿童ITP的发病有密切相关性。［中国当代儿科杂志,2009,11（12）：999-1001］