Platelet proteins as autoantibody targets in idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP), caused by autoantibodies directed against certain platelet antigens, is the most common entity of the immune thrombocytopenias. ITP is an acquired disorder and can affect both children and adults. However, the clinical syndromes of ITP are distinct between children and adults. Childhood (acute) ITP characteristically is acute in onset, occurs within 1-2 weeks of an infection, usually of viral origin, resolves spontaneously within 6 months. Adult (chronic) ITP has an insidious onset and rarely resolves spontaneously. Over the last decade considerable new information has accumulated as to the pathophysiological mechanisms of immune thrombocytopenias. In addition, most of the knowledge on this disorder has been obtained from studies of adult patients with chronic ITP. The present work gives an updated overview of the platelet autoantigens and the molecular immunological reactions in ITP.     

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.     

Role of complement in immune or idiopathic thrombocytopenic purpura

The clinical course of immune or idiopathic thrombocytopenic purpura (ITP) is variable, suggesting different mechanisms for the decreased platelet count. The complement factors C3 and C4 have been detected on platelets, both alone and in association with immunoglobulin G (IgG), and a reduced platelet survival time has been described. Platelets have the capacity to interact with the complement system since they have both complement receptors and complement regulatory proteins on their cell membranes. The membrane attack complex (C5b-9) induced by antiplatelet antibodies generates platelet microparticles in a concentration-dependent manner. A marked variation in resistance to this phenomenon has been demonstrated between individuals and between men and women. These platelet microparticles seem to retain their biological role in haemostasis. Platelets also appear to play a role in the processing of immune complexes. Immunoglobulins and complement factors are found in several clinical situations where circulating immune complexes are expected. Furthermore, human platelets bind immune complexes in vitro and the reaction can be blocked by antireceptor antibodies to immunoglobulins and complement. These findings raise a number of questions about the role of complement in the pathophysiology of ITP.     

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.     

Isolated thrombocytopenia in children: thinking beyond idiopathic thrombocytopenic purpura and leukaemia

The commonest cause of isolated thrombocytopenia in an otherwise well child is idiopathic thrombocytopenic purpura (ITP). The inherited thrombocytopenias such as Bernard-Soulier syndrome are rare but often misdiagnosed as ITP owing to a similar clinical presentation. We describe a child with Bernard-Soulier syndrome who presented with isolated thrombocytopenia, mimicking ITP. Features which help to differentiate these two conditions are discussed with a brief literature review.     

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目的探讨影响小儿急性特发性血小板减少性紫癜(AITP)发展成慢性特发性血小板减少性紫癜(CITP)的危险因素。方法选择2006年5月至2010年4月于广西医科大学一附院诊断AITP住院患儿138例,对患儿临床表现、实验室检查、治疗方案等16个相关因素分别进行单因素成组对照研究。对有意义的单因素,再运用非条件Logistic多因素回归模型分析,以期找到有意义的因素。结果病程(患儿起病至治疗时间)、ORh(D)+型血、用含有大剂量丙种球蛋白的治疗方案、血小板上升正常时间都是影响AITP患儿转为慢性的主要因素,而与发病年龄、治疗初用血小板、血小板开始回升时间、性别、有无前驱显性感染、治疗前血小板数、血小板平均体积、血小板平均分布系数、骨髓巨核细胞数、幼稚巨核细胞数、颗粒型巨核细胞数、有无幼稚淋巴细胞数无关。结论 AITP患儿早期治疗时用有大剂量丙种球蛋白的治疗方案是改善预后的关键,治疗时血小板回升正常时间晚、ORh(D)+血型(相对于A和B血型)是转为慢性的高危因素。     

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.     

Treatment of childhood idiopathic thrombocytopenic purpura with Rhesus antibodies (anti-D)

We have recently reported that a rise of platelet numbers in ITP can be induced by blockade of the RES with antibody-coated red blood cells. We now present a collaborative study in which 15 Rhesus-positive children with ITP (nine boys and six girls aged 1–15 years) were treated with low-dose anti-D. Ten patients had chronic ITP (duration 6–47 months), five had acute ITP. Doses of 28–50 g anti-D/kg bodyweight per course were given intravenously. In all patients clinical signs of bleeding ceased and platelet counts were elevated. An excellent, good or fair response with platelet increments of >100, 50–100, or 20–50×10⁹/l, respectively, was observed in 19, 7, and 12 out of 45 courses in chronic ITP, and in 4, 1, and 2 out of 8 courses in acute ITP. The platelet increase (>40×10⁹/l) persisted for 10 to over 360 days in chronic ITP. There were no untoward side reactions. Haemoglobin values remained stable in all patients but laboratory signs of mild, compensated haemolysis ensued. The direct antiglobulin test became positive in all cases due to anti-D IgG. Previous therapy of patients with chronic ITP included high-dose immunoglobulins and prednisone. These regimens were both effective but remissions were short. We conclude that anti-D therapy is an effective and safe form of treatment in childhood ITP.Abbreviations ITP idiopathic thrombocytopenic purpura - IgG immunoglobulin G - RES reticuloendothelial system - RBC red blood cells - Rh Rhesus - DAT direct antiglobulin test     

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。     

特发性血小板减少性紫癜患者血小板抗体及淋巴细胞亚群的研究

目的探讨血小板相关抗体(PAIgG)和T淋巴细胞亚群的变化,在特发性血小板减少性紫癜(ITP)免疫发病机制中的作用、临床意义。方法采用间接免疫荧光法测定30例ITP患者及20例正常对照组的PAIgG,20例ITP患儿治疗后复查PAIgG。同时采用流式细胞仪直接免疫荧光法检测外周T血淋巴细胞亚群。结果ITP组PAIgG阳性率为80%,正常对照组为20%(P<0.001),ITP组PAIgG明显高于正常对照组(P<0.001),20例ITP患儿治疗后复查PAIgG,其数值明显下降,差异有显著性(P<0.001)。T淋巴细胞亚群中,ITP组CD3、CD4、CD4/CD8显著低于正常对照组(P<0.01),CD8则显著高于正常对照组(P<0.01)。结论抗血小板相关抗体对提高ITP的诊断、疗效及预后的判断有一定的实用价值,T淋巴细胞亚群的变化能较好的反映ITP的病理机制。     

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.     

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.     

Presence of platelet antibodies in idiopathic thrombocytopenic purpura may discriminate acute from chronic disease

This study estimated the prevalence of serum antibodies against thrombocyte glycoproteins, at disease onset (54 patients) and later on during the course of the disease (71 patients), in sera from children with idiopathic thrombocytopenic purpura (ITP). Only a minority had serum antibodies at disease onset, with a significantly higher frequency in those who developed the acute form of the disease than in those who developed the chronic form. Serum antibodies may persist after spontaneous cure of acute disease. There was no switch from immunoglobulin M (IgM) to IgG antibodies over time. CONCLUSION: The pathogenesis of the acute and chronic forms of ITP may be different.     

Role of myeloid human cytomegalovirus infection in children's idiopathic thrombocytopenic purpura

This project explores the specificity of myeloid human cytomegalovirus (HCMV) infection in pathogenesis of idiopathic thrombocytopenic purpura (ITP). Eighty-one subjects with ITP were observed. HCMV early antigen and related myeloid cells in bone marrow, and platelet, HCMV IgM, and IgG in blood were tested. The results presented potent evidence that myeloid HCMV infection is a specific factor in children's ITP: patients of ITP with myeloid HCMV infection had a tendency for exacerbation, refractoriness, and chronic advance. However, HCMV did not affect the quantity of megakaryocyte, which showed the complicated relationships between HCMV and ITP.     

小儿特发性血小板减少性紫癜急性至慢性的危险因素分析

目的探讨影响小儿急性特发性血小板减少性紫癜(AITP)发展成慢性特发性血小板减少性紫癜(CITP)的危险因素。方法选择120例AITP患儿进行成组设计的病例对照研究。进行单因素分析后运用多因素非条件Logistic回归模型分析。结果在α=0.05水平,45项指标中单因素分析共筛选出有统计学意义的因素12项,分别是:家住农村、生后非纯母乳喂养、既往有反复呼吸道感染史、病初白细胞数低或正常、发病时年龄大、治疗前病史长、发病时体重大、病初骨髓巨核细胞总数高、原始幼稚巨核细胞数高、颗粒型巨核细胞数高、治疗后血小板开始上升时间长、血小板峰值低。进入非条件Logistic多因素回归模型的变量有6个,按照其对AITP预后影响危险性的大小依次为:治疗前病史(OR=13.46,95%CI3.194～56.730)、发病时年龄(OR=11.90,95%CI2.279～62.085)、病初白细胞数(OR=10.43,95%CI1.947～55.915)、发病时体重(OR=1.10,95%CI1.013～1.194)、病初骨髓巨核细胞数(OR=1.01,95%CI1.005～1.020)、治疗后血小板峰值(OR=0.10,95%CI0.991～0.999)。结论AITP患儿初诊时进行骨髓巨核细胞检查,在治疗过程中观察最大血小板数对预后的判断有重要价值。早诊断、早治疗有利于改善预后。     

Incidence of thrombocytopenia in infants born to mothers with idiopathic thrombocytopenic purpura

Abstract Neonatal thrombocytopenia related to maternal idiopathic thrombocytopenic purpura (ITP) is reportedly uncommon but may have severe complications. The present report reviews records of 15 infants born to mothers with ITP during a 10-year period, and the incidence of neonatal thrombocytopenia and the risk of hematological complications is examined. Severe thrombocytopenia (platelets < 50 000/μL) was seen in three infants despite successful therapy with high-dose gamma globulin prior to delivery, which elevated maternal platelet counts. Although the platelet counts of these three infants fell to < 10 000/μL, none had severe complications. Moreover, no infants required treatment such as adrenocorticosteroids, platelets transfusion, or high doses of gamma globulin. No maternal markers predicted the degree of neonatal thrombocytopenia. The risk of complications arising from neonatal thrombocytopenia is low, but careful observation is required for the thrombocytopenic newborn of ITP mothers even when the infant has no bleeding complications at delivery.     

Spontaneous bilateral hemotympanum in idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura is a condition frequently encountered in childhood. Extensive literature currently exists on its etiology and management. Petechiae, ecchymoses and epistaxis are the usual manifestations of this condition, originating from the autoimmune destruction of platelets. Bleeding may occur spontaneously from any mucosal membrane. While bilateral hemotympanum has yet to be documented as a possible complication of this condition, immediate impact on the child’s hearing will require appropriate follow-up.