大剂量短疗程泼尼松治疗儿童急性免疫性血小板减少症的疗效观察

目的观察大剂量短疗程泼尼松(Pred)疗法对儿童急性免疫性血小板减少症(ITP)的疗效。方法 162例ITP患儿根据治疗方法不同随机分为大剂量静脉丙种球蛋白+甲基泼尼松龙组(IVIG+MP)、静脉丙种球蛋白组(IVIG)、甲基泼尼松龙组(MP)与Pred组。IVIG+MP组41例,采用IVIG(1g/kg,共1次)+MP[10 mg/(kg.d),每3天减半量,共9 d]冲击治疗,继之口服Pred[1.5～2.0 mg/(kg.d)],并逐渐减量维持治疗;IVIG组39例,采用丙种球蛋白(1 g/kg,共1次)冲击治疗,继之口服Pred[1.5～2.0 mg/(kg.d)]并逐渐减量维持治疗;MP组40例,采用MP[10 mg/(kg.d),每3天减半量,共9 d]冲击治疗,继之口服Pred[1.5～2.0 mg/(kg.d)]并逐渐减量维持治疗;Pred组42例,采用口服Pred[4 mg/(kg.d),共4 d]治疗后停药,无减量维持治疗。比较各组治疗前后血小板数、治疗有效率、不良反应发生率及药费支出。结果各治疗组治疗前后血小板数及治疗有效率差异无显著性,IVIG+MP组、IVIG组、MP组治疗不良反应发生率及药费支出均高于Pred组。结论大剂量短疗程Pred疗法治疗儿童急性ITP能有效提升血小板计数,有效率与IVIG及MP冲击治疗相比差异无显著性,不良反应少,花费低。     

Current management issues of childhood and adult immune thrombocytopenic purpura (ITP)

The management of acute and chronic immune thrombocytopenic purpura (ITP) of children differs in many aspects from that of adults. Current paediatric and adult treatment options are discussed in this review in the light of the recently published practice guidelines for the diagnosis and treatment of ITP issued by a panel of paediatric and adult haematologists on behalf of the American Society of Hematology. Uncontrolled rather than controlled randomized studies often represent the basis for treatment decisions. Important issues in improving the management of patients with ITP include the identification of research priorities resulting in controlled clinical trials with well-defined study endpoints, the logistics and coordination of research activities and their presentation at international meetings.     

Recurrent immune thrombocytopenic purpura in children

Recurrent immune thrombocytopenic purpura (ITP) is defined as the recurrence of ITP after at least 3 months of remission sustained without treatment. Among 340 children with ITP, 14 had recurrent ITP (4.1%). Ten were females. The initial course was acute in 8 patients and chronic in 6. The median time to recurrence was 33 months (range 4-120). Only 1 patient had a second recurrence. Twelve (86%) achieved complete (n = 10) or partial (n = 2) remission, two of them after splenectomy. One patient continued to require treatment at 10 months from recurrence. One child died of intracranial hemorrhage despite aggressive treatment including splenectomy and craniotomy.     

HLA frequencies and haplotypes in children with idiopathic thrombocytopenic purpura (ITP)

26 patients with an acute reversible ITP and 6 with chronic ITP were tissue typed, together with their healthy first-degree relatives. The HLA frequencies of the different groups were compared with those of a normal control population. The only significant difference between the groups was an increase in the frequency of Aw32 in acute ITP patients. HLA-Aw32 was present in 26.9% of patients, but in only 0.8% of the controls (corrected P=0.000027). The possible importance of associations between antigens of the HLA-A locus with certain diseases are discussed. Family analyses and haplotype determinations proved to be unproductive because no familial clustering of ITP was found.     

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.     

A cost-utility analysis of treatment for acute childhood idiopathic thrombocytopenic purpura (ITP)

BACKGROUND: The primary objective in the treatment of acute pediatric idiopathic thrombocytopenic purpura (ITP) is to rapidly increase the platelet count. METHODS: We built a decision analytic model to evaluate the cost-utility of four commonly used treatment strategies: intravenous immunoglobulin G (IVIG) 0.8 g/kg, anti-D 75 mcg/kg, methylprednisolone (30 mg/kg for 3 days), and prednisone (4 mg/kg/day for 4 days). In our baseline model, all children were hospitalized upon presentation, and discharged once the platelet count reached > or =20,000. We performed a literature search to estimate time to platelet count > or =20,000 for each strategy, as well as the probability of side effects. We obtained cost data and quality of life measures from institutional and published data sources. RESULTS: Total cost of one-time treatment for a 20 kg child was US dollars 786 with prednisone, US dollars 1,346 with methylprednisolone, US dollars 2,035 with anti-D, and US dollars 2,492 with IVIG. The strategies of IVIG and methylprednisolone were less effective and more expensive than anti-D and prednisone, respectively. Although anti-D caused the most rapid rise in platelet counts, the incremental cost-utility ratio (costs incurred by using anti-D instead of prednisone divided by health benefit of using anti-D instead of prednisone) was US dollars 7,616 per day of severe thrombocytopenia avoided, primarily due to the much higher medication cost of anti-D. Utilizing an outpatient model, the cost difference between anti-D and prednisone was even more striking. CONCLUSIONS: The clinical benefit of anti-D is offset by a substantial cost increase. Although often overlooked in favor of newer agents, a brief course of high-dose prednisone is an inexpensive and effective treatment for acute ITP.     

Intravenous immune globulin versus intravenous anti-D immune globulin for the treatment of acute immune thrombocytopenic purpura

Objective  The purpose of this study was to compare the efficacy and side effects of intravenous immunoglobulin (IVIG) with intravenous anti-D immunoglobulin for treatment of newly diagnosed acute childhood Idiopathic thrombocytopenic purpura (ITP). Methods  Children (6 months to 14 years) with newly diagnosed acute ITP and platelet count below 20,000/ μL were randomized to receive single dose intravenous 75 μg/kg anti-D or 1g/kg IVIG for two consecutive days (total dose 2 g/kg). Response rate defined as a platelet count over 20,000 / μL 72 hours after initial treatment. Results  Eighty one patients (52 male and 29 female) with mean age of 5 years and 3 months randomly divided in anti-D group (n=42) and IVIG group (n=39). Mean baseline (pretreatment) platelet counts were 15406 / μL and 15230/ μL in anti-D and IVIG group, respectively. The response rate in IVIG group (98%) was more significant than anti-D group (76%); (P = 0.017). After 7 days the platelet counts of all patients in IVIG group were more than 20,000/ μL while in anti-D group 12% had platelet counts below 20,000/ μL. Conclusion  In acute childhood ITP, initial treatment with IVIG (2g/Kg in divided dose) increased platelet count more rapidly and more significant than intravenous anti-D (single dose of 75 μg/Kg) within the first 72 hours.     

小儿特发性血小板减少性紫癜的有关临床特点

目的探讨小儿特发性血小板减少性紫癜(ITP)的临床特点。方法对我院收治的255例ITP患儿的临床资料进行分析。结果1、男:女=1.43,中位年龄31个月,2岁以下占47.06%;急性型占91.37%,慢性型占8.63%。2、47.84%有前驱感染病史,31.76%在发病前1~4周有预防接种史。3、病原学检查阳性率73.81%,其中HPVB1945.24%。4、预防接种疫苗中乙肝疫苗34.57%,百白破疫苗24.69%,麻疹疫苗8.64%。5、临床表现94.12%以轻、中度皮肤粘膜出血为主,重度出血仅占5.88%。6、就诊时血小板数量:平均22.47×109/L,≤20×109/L占56.47%。7、骨髓常规涂片巨核细胞总数增多的占77.06%,分类中成熟无血小板产生的巨核细胞数>原始幼稚巨核细胞数>成熟有血小板产生的巨核细胞数>裸核巨核细胞数。8、给予以肾上腺皮质激素为主的治疗,97.42%血小板在2周内达正常,复发率4.29%。9、疫苗相关ITP的中位年龄6月,就诊时平均血小板数量22.3×109/L,95.06%患儿为轻中度出血;骨髓巨核细胞数增多者占75.68%;病原学检查阳性率为85.71%,其中HPVB19占64.29%;93.83%患儿治疗后平均4.90天血小板恢复正常水平,复发率3.7%。结论1、小儿ITP患者大多数为急性型,预后良好。2、病毒感染与小儿ITP关系密切,HPVB19在小儿ITP发病中有重要意义。3、疫苗相关的ITP发生率高于以往报道,除发病年龄小外临床特点与其他ITP相似,相关疫苗中以乙肝、百白破疫苗多见,应引起注意。4、HPVB19阳性患儿临床特点与一般ITP大致相同。5、以肾上腺皮质激素为主的治疗方案治疗小儿ITP疗效显著;大剂量丙种球蛋白和大剂量肾上腺皮质激素对有严重出血或血小板极低的患儿止血效果明显,可以避免血小板输注和相关死亡的发生。     

Treatment of an infant with severe acute refractory immune thrombocytopenic purpura using combination therapy including rituximab

Some infants with acute immune thrombocytopenic purpura (ITP) do not respond to first‐line therapy, and currently there is no consensus on therapy for these refractory cases. We describe a 12‐week‐old infant with acute ITP who was unresponsive to intravenous immunoglobulin and corticosteroid, and developed gastrointestinal bleeding. Several combination therapies were unsuccessful. After four doses of rituximab followed by intravenous immunoglobulin and corticosteroid, his platelet counts gradually increased. Combined therapy which includes rituximab may be a promising treatment for severe acute refractory ITP. Pediatr Blood Cancer 2009;53:203–205. © 2009 Wiley‐Liss, Inc.     

Incidence of childhood primary immune thrombocytopenic purpura

There is a discrepancy in the reported incidence of childhood immune thrombocytopenic purpura (ITP) between Europe (2.9–5.3 per 100 000 persons) and Japan (1.91). Ise district is a suitable area in which to conduct epidemiological study because there is little fluctuation in the sociodemographic factors. We performed a retrospective population‐based study to clarify the incidence of primary childhood ITP. We calculated person‐years for children aged <15 years based on the Ise district demographics between 2002 and 2012. The calculated person‐years were 298 533. The number of hospitalized patients in Ise district was 25 (M/F, 14/11) during the study period. The calculated incidence was therefore 8.4 per 100 000 person‐years. It is possible that the difference in incidence between the present calculation and that of the European studies is due to variation in accuracy and/or registration criteria between the studies.     

Retrospective evaluation of children with immune thrombocytopenic purpura and factors contributing to chronicity

ObjectiveImmune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia children. The aim of this retrospective study is to describe presenting features and clinical characteristics of ITP and evaluate clinical course, treatment modalities, and complications and determine the effects of preceding infection history, age, gender, treatment modality, and admission platelet count on chronicity.MethodTwo hundred and eleven patients who were diagnosed ITP and followed-up in Department of Pediatric Hematology, Ankara Children Hematology Oncology Education and Research Hospital between January 2008 and September 2012 were included. Age of the patients, gender, date of admission, date of diagnosis, complaint in the application, previous infection and laboratory tests were recorded.ResultsMean age of the patients on diagnosis was 5.4 ± 4.1 years. The female/male ratio was 1.03. The clinical courses were determined as acute or chronic in 72% and 28% of patients respectively. Mean age at diagnosis was significantly higher in chronic ITP (p < 0.01). Chronic course was significantly higher in female patients (p < 0.05). The most frequent complaint was bruises on the skin (68%). The most common physical examination findings were petechiae, purpura and ecchymosis (89%). Patients with a history of past infection (53.6%) and who had serologically positive infection (15.6%) frequently had acute course (p < 0.01). The most common serologically positive infection was Rubella. The mean platelet count was significantly higher in chronic ITP (p < 0.01). In the initial treatment of patients admitted in the acute phase, megadose methylprednisolone (MDMP) was used in 31% of patients, intravenous immune globulin (IVIG) in 55% of patients and anti-D in 2% of patients while 12% did not receive any treatment. There were no significant differences between the recurrence rate and treatment modality (p > 0.05).ConclusionIn our study, in females and in patients without any history of past infection, platelet count >20 × 10⁹/L and initial diagnosis age > 10 years were found to increase the probability of chronic disease, which is compatible with the literature.     

Directions for research in autoimmune thrombocytopenic purpura (ITP)

All attendees participated in a round-table discussion regarding directions for research in autoimmune thrombocytopenic purpura (ITP). Suggested areas for study were grouped into five main areas: (i) improved classification of ITP identifying subsets of patients with differing clinical syndromes and response to treatment, and those more likely to have serious bleeding manifestations; identification of patients with reduced thrombopoiesis was emphasized; (ii) studies aimed at elucidating the aetiology and pathophysiology of ITP, with emphasis on distinctions between acute and chronic ITP and between patients responsive or refractory to therapy; these studies focused on measures of humoral and cellular immune dysregulation; (iii) studies of platelet function in ITP, with the intent of defining these abnormalities and correlating them with the clinical manifestations of the disease; (iv) new approaches to treatment, particularly of refractory patients; and (v) a miscellaneous group, which included development of an ITP registry, evaluation of the "burden" of disease, investigation of mood changes in ITP, etc. The discussion was not intended to be all-inclusive, but focused on the content of other talks in this symposium. It is hoped that some of thesesuggestions will be further developed for investigation in multicentre co-operative studies to improve the diagnosis, understanding and treatment of ITP.     

Cytokines in idiopathic thrombocytopenic purpura (ITP)

Most research in idiopathic thrombocytopenic purpura (ITP) has focused on characterization of the autoantibodies directed against platelet antigens resulting in enhanced platelet elimination by macrophages. This report summarizes the current knowledge of cytokine pattern found in individuals with ITP. Serum assessment has demonstrated increased levels of interleukin (IL)-2 and interferon-gamma (IFN-7), while IL-4 was significantly decreased. In addition, thrombopoietin (TPO) has been found in normal levels while IL-11 has been reported to be elevated. These data indicate that ITP is associated with a Th1 type of T helper cytokine response, while that of type Th2 is downregulated. Initially, megakaryocytes are found at normal levels in bone-marrow aspirates, explaining the unchanged production of TPO. The increase in IL-11 may be reflected by the increased number of platelets being produced per megakaryocyte. However, there is little information on these events in immunocompetent sites such as bone marrow, spleen and lymph nodes.     

Idiopathic thrombocytopenic purpura (ITP): a historical odyssey

Purpura has been recognized since ancient times and its clinical syndromes were refined by important observations in the sixteenth, seventeenth and eighteenth centuries. It required the development of adequate microscopes in the nineteenth century, however, to recognize the platelet, leading to the recognition of the thrombocytopenic component of ITP. The twentieth century brought recognition of the pathophysiology of the disorder and further defined the clinical states and treatments for ITP. The latter half of the twentieth century has focussed on the autoimmune components of ITP, initially on the humoral immune aspects and more recently on dysregulation of cellular immunity.     

Epstein-Barr virus associated with immune thrombocytopenic purpura in childhood: a retrospective study

OBJECTIVE: Although Epstein-Barr virus (EBV) is known to cause immune thrombocytopenic purpura (ITP), the epidemiology of this pathogen in children with ITP is not known. In the present study, the clinicoepidemiology and laboratory characteristics of EBV-associated ITP in childhood were analysed retrospectively. METHODS: The study cohort consisted of 108 children in whom ITP was diagnosed between 1990 and 1998. Patients were divided into EBV or non-EBV groups according to their serological status at diagnosis. RESULTS: Thirty-five (32.4%) of 108 children had ITP associated with acute EBV infection. The clinical manifestations and laboratory data were similar in children with and without acute EBV. Responses to various modalities of therapy were analysed. The average time to achieve complete remission (platelet count > or =150 x 10(9)/L) in EBV and non-EBV groups was 26 and 16 days, respectively. CONCLUSIONS: The incidence of childhood ITP associated with acute EBV infection is relatively high in Taiwan. Patients with EBV-associated ITP tended to resolve more slowly than those without EBV infection.     

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.     

Intended management of children with acute idiopathic thrombocytopenic purpura: a national survey

OBJECTIVE: In Australia acute idiopathic thrombocytopenic purpura (ITP) is mainly treated by paediatricians (either general paediatricians or paediatric haematologists/oncologists). A survey was conducted to gauge the current practice of treating children with acute ITP in Australia. METHODS: All practising Australian paediatricians registered by the Royal Australasian College of Physicians were surveyed regarding their intended management of children with acute ITP. The questionnaire, adapted from a study of paediatric haematologists/oncologists in North America, presented four clinical scenarios of children with acute ITP with a platelet count of 3000 x 10(9)/L, with and without mucosal bleeding (wet and dry purpura, respectively). Questionnaires were returned by mail or filled in online at a dedicated webpage. RESULTS: Five hundred and sixty-three of 1097 (51%) paediatricians responded to the survey. Data from 140 who had treated at least one child with ITP in the previous 12 months were analysed. Respondents indicated that children with acute ITP are usually or always hospitalised (58-92%) and that 48% would be given active treatment, even with dry purpura. Various regimens of i.v. immunoglobulin or corticosteroids are used when treatment is administered. In comparing Australian and North American management of acute ITP there were many similarities, although Australian paediatricians were less likely to arrange a bone marrow aspirate if corticosteroids were prescribed. CONCLUSIONS: There is great variation in the intended management of children with acute ITP in Australia. Previously published management recommendations regarding investigation and treatment have had little impact on intended practice. Prospective studies are required to evaluate hypotheses so as to produce evidence-based recommendations for treatment of patients with acute ITP.     

Increase in platelet count following short course therapy with recombinant alpha-2b-interferon in immune thrombocytopenic purpura in childhood

Two boys, aged three and seven years with immune thrombocytopenic purpura continued to show platelet counts below 20, 000/mm³ inspite of treatment with high dose gammaglobulin and steroids. Alpha-2b-in-terferon injections were followed by normalisation of platelet counts in both patients. No side effects were seen. Alpha-interferon may be a safe and effective treatment for childhood-ITP.