儿童慢性特发性血小板减少性紫癜的临床转归

目的总结儿童慢性特发性血小板减少性紫癜(cITP)的临床经过及主要临床特点,以期对儿童cITP的应对策略有所帮助。方法回顾性分析58例儿童慢性ITP的自发缓解情况与主要临床特点。结果(1)58例cITP患儿中,33例(56.9%)获得自发缓解,中位缓解时间1年;预计累计自发缓解率在诊断后6~12个月、2、3和4年内分别为40%,47%,47%,55%,无死于出血者。(2)儿童cITP的起病年龄、性别、前驱感染史、病初PLT、抗核抗体及病初对药物治疗的反应均与疾病转归无关(P≥0.05)。(3)急、慢性ITP患儿的最低血小板计数分布基本相同(P=0.156),轻、中度出血的分布没有差别(P=0.329),但cITP重度出血多于急性ITP,分别为13.8%和1.9%。结论儿童cITP中的部分病例也呈现自限性经过,起病时的临床表现及早期药物治疗对疾病转归无明显影响。     

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.     

Steroid-free interval with anti-D in chronic idiopathic thrombocytopenic purpura

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the antibody-mediated destruction of platelets. To maintain the platelets above the symptomatic level we administered 100 μg of anti-D for 5 consecutive days to 19 children with ITP. Four patients did not respond to the treatment. Fifteen responded with an increase in the average platelet number to 76 000/μL 7 days postinjection. However, the platelet count dropped within 45 days to 27 000/μL. Three months after this study, two patients from the study group were then administered monthly anti-D after reinjecting anti-D daily for 5 consecutive days, as previously performed. Platelet levels in these two patients were maintained above 30 000/μL for 5 and 6 months respectively. We concluded that anti-D administration for 5 consecutive days can induce an increase in platelets followed by a decrease below 30 000/μL after 30–45 days. However, monthly administration of anti-D after daily injections for 5 consecutive days can keep platelets above the symptomatic level and may provide a corticosteroid-free safe interval for nearly 5 months.     

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.     

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。     

儿童特发性血小板减少性紫癜血小板功能研究

目的研究儿童特发性血小板减少性紫癜(ITP)血小板体内活化状态及体外活化功能,探讨血小板在ITP发病机制中的作用。方法流式细胞术(FCM)检测体内和体外5’-二磷酸腺苷(ADP)刺激后血小板表面活化分子GPIIb/IIIa和CD62P分子的表达,同时检测CD62P阳性血小板该分子的平均荧光强度(MCF)。结果ITP组与对照组体内活化血小板百分比有显著性差异(P=0.0001),ITP组显著低于对照组;两组CD62P分子的MCF无显著性差异。体外刺激血小板活化后,两组活化血小板百分比有显著性差异(P=0.0077),ITP组低于对照组;两组CD62P分子的MCF有显著性差异(P=0.0059),ITP组低于对照组。结论ITP患儿体内血小板处于低活化状态,提示其出血原因不仅是血小板数量减少,同时存在血小板功能减低,低活化的原因很可能是血小板自身功能障碍。     

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.     

Anti-D immunoglobulin in the treatment of idiopathic thrombocytopenic purpura

Anti-D was evaluated in 8 RhD positive patients (6 males, 2 females) aged 2–21 years (mean 10 years) with idiopathic Thrombocytopenic Purpura (ITP). Five patients with chronic ITP and 3 patients with acute ITP were administered Anti-D in the dosage of 50 ug/kg intramuscularly (IM) for 3 consecutive days. One patient of chronic ITP received two courses of Anti-D. Patients were followed up for 7 to 16 months (mean 9 months). All three cases of acute ITP had a complete response and are in remission between 3 to 12 months of follow up. Two of five cases of chronic ITP had a partial response. Rise in platelet count was observed within 72–124 hours, and duration of response varied between 10 to 15 days. None of these patients had any significant side effects of anti-D immunoglobulin therapy. Intramuscular administration of anti-D is safe, effective and low cost alternative to IVlgG in the treatment of acute ITP.     

Role of the T cell receptor in idiopathic thrombocytopenic purpura (ITP)

During the past few decades a number of studies has described T cell defects and attempted to elucidate their role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Some studies implicate T cells as potential initiators of autoantibody production in ITP. However, only a few of these have studied the role that the T cell receptor may play in the pathogenesis of ITP. In a variety of autoimmune syndromes interest has focused on the α- and β-chains of the T cell receptor. Deviations from the normal T cell receptor gene usage have been reported in rheumatoid arthritis, systemic lupus erythaematosus and multiple sclerosis. Usually, these studies have shown a restricted heterogeneity of T cell receptor variable gene usage. The studies on the T cell receptor in ITP have included a limited number of patients, which makes it difficult to evaluate the significance of the role that the T cell receptor may play in the pathogenesis of ITP. Further studies are warranted.     

幽门螺杆菌感染与儿童特发性血小板减少性紫癜

特发性血小板减少性紫癜(ITP)是以自身抗体介导的血小板破坏为特征的一组疾病,近年来许多研究显示部分成年人ITP的发生与幽门螺杆菌(Hp)感染密切相关,清除Hp后ITP患者的血小板数量有明显提高.研究认为Hp相关的ITP与抗原交叉反应有关,但其确切机制目前尚不明确;儿童ITP是否需要清除Hp治疗,国内外也存在争议.     

病毒感染与慢性特发性血小板减少性紫癜

目的为探讨病毒感染与慢性特发性血小板减少性紫癜(CITP)的关系。方法选择32例CITP患者(年龄8个月~13岁,男13,女19)及30例健康查体正常对照儿童(年龄1岁~14岁,男14,女16)。采用间接ELISA法测定两组血清巨细胞病毒(CMV)、肝炎病毒[包括乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)]和人类疱疹病毒(HHV)相关抗体。结果慢性ITP患儿各种病毒相关抗体阳性率高于对照组,其中巨细胞病毒抗体阳性率两组间比较差别具有显著性意义(P<0·05)。结论①慢性反复性病毒感染可能是导致ITP反复发作的重要原因之一,②临床上对ITP患者特别是慢性ITP患者应该常规进行病毒学实验室检查,有助于判断预后,指导治疗。     

特发性血小板减少性紫癜血小板参数变化及其临床意义

目的探讨特发性血小板减少性紫癜(ITP)时血小板参数的变化及其临床意义。方法对确诊为急性型特发性血小板减少性紫癜患儿67例分别测定其治疗前后的血小板数(PLT)、平均血小板体积(MPV)及血小板分布宽度(PDW)及大血小板比率(P-LCR),同时测定50例健康儿童以上血小板参数作为对照组。治疗前与对照组及与治疗后分别进行比较。并对血小板与血小板参数进行相关性分析。结果(1)ITP患儿治疗前PLT明显低于对照组,而PDW、MPV、P-LCR明显高于对照组,差异均具有极显著性(P<0·001),治疗后PLT上升,PDW、MPV、P-LCR下降,与治疗前比较差异具有极显著性(P<0·001)。(2)ITP轻、中、重度患儿随病情加重PLT进行性下降,而PDW、MPV、P-LCR进行性增大,但极重度患儿MPV反而变小。(3)PLT与MPV呈负相关(P<0·001)。MPV与PDW、PDW、MPV与P-LCR、PDW与P-LCR呈正相关(P<0·05)。结论血小板参数的动态观察有助于ITIP的鉴别诊断、病情判断及疗效观察。     

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.     

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。     

个体化剂量丙种球蛋白联合地塞米松治疗儿童重症特发性血小板减少性紫癜78例疗效观察

目的观察个体化剂量静脉注射用丙种球蛋白(IVIG)联合地塞米松治疗儿童特发性血小板减少性紫癜(ITP)的疗效。方法重症ITP患儿入院后均给地塞米松及IVIG[400 mg/(kg.d)],3 d后测外周血血小板计数,≥100×109/L停用IVIG,继用地塞米松;若<100×109/L,再继续用原剂量IVIG 2 d。结果治疗3 d后,78例患儿中,37例外周血血小板计数升至100×109/L以上,余41例继续治疗后,31例升至100×109/L以上。结论个体化剂量IVIG联合地塞米松是治疗儿童重症ITP的有效办法,可节省一定医疗费用。     

High doses of gamma globulin and methylprednisolone therapy for idiopathic thrombocytopenic purpura in children

In four children with chronic idiopathic thrombocytopenic purpura (ITP), high doses of gamma globulin or methylprednisolone were effective in increasing platelet counts transiently, yet there was no quantitative relationship between the platelet responses to these two therapies. This finding suggests a qualitative difference in the mechanisms of increasing platelets by the two drugs. High doses of gamma globulin and methylprednisolone showed a synergistic effect on the initial and maximal platelet responses, suggesting an intensification of the effect of gamma globulin by methylprednisolone. This combination therapy should be clinically useful, particularly in the control of acute haemorrhage or in preparations for emergency surgery.Abbreviation ITP idiopathic thrombocytopenic purpura Offprint requests to: Department of Pediatrics, Faculty of Medicine, Kyushu University, 60, 3-1-1, Maidashi,Higashiku, Fukuoka, 812, Japan     

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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。     

Randomized trial comparing intravenous immunoglobulin with methylprednisolone pulse therapy in acute idiopathic thrombocytopenic purpura

Forty-three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (PC) below 20 × 10⁹ 1⁻¹, and either continued bleeding or failure to show a spontaneous rise in the PC after a 3 day observation period were randomized to treatment with either intravenous immunoglobulin (IVIG) infusions I gkg⁻¹ (n = 23) or intravenous methylprednisolone pulse therapy (MPPT) 30mgkg¹ (n = 20) on two consecutive days. After 72h, IVIG had induced greater platelet responses (mean PC 188 × 10⁹ versus 77 × 10⁹1⁻¹ 2p < 0.001) and raised the PC to a haemostatically safe level above 50 × 10⁹1⁻¹ more frequently (91 versus 50%, one-sided e×act p = 0.003). Children responding poorly were then given the alternative treatment in addition. After 6 days, a normal PC of over 150 × 10⁹1⁻¹ had been obtained more frequently in the group given first-line IVIG (70 versus 50%, p = 0.16). The relapse rates during 6 months of follow-up were not significantly different (26 versus 40%, p = 0.26). Cross-over treatment in 11 children with relapse confirmed the superior response to IVIG. The treatment given was restricted to the two initial infusions more often in the IVIG group (70 versus 35%, p = 0.05). These results indicate that IVIG may be preferable to MPPT as the initial treatment for ITP.     

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.