儿童慢性特发性血小板减少性紫癜免疫紊乱与治疗

目的探讨儿童慢性特发性血小板减少性紫癜(1TP)自身免疫的病理机制,以及α-2b干扰素的治疗效果。方法慢性ITP组18例,健康儿童17例,均采用流式细胞术检测外周T淋巴细胞亚群,以及免疫荧光抗体双标记法检测单个核细胞内Th1/Th2细胞因子的表达情况;18例慢性ITP病人均给予α-2b干扰素治疗,总疗程3个月。结果儿童慢性ITP患者存在T淋巴细跑表型及功能异常,其外周血CD4+减少,CD8+升高,CD4+/CD8+明显降低;且Th1/Th2功能失衡,是一种Th2优势疾病。本组18例应用α-2b干扰素治疗,其中显效6例,良效4例,进步3例,无效5例。结论儿童ITP是一种自身免疫性疾病,T淋巴细胞表型和功能异常在慢性ITP的发病中起重要作用。α-2b干扰素治疗可使患儿Th1细胞因子产生增加,而Th2细胞因子产生减少,因而抑制B淋巴细胞产生抗血小板抗体;α-2b干扰素价格低廉,毒付作用轻,应用方便,为儿童慢性ITP开辟了另一条治疗途径。     

特发性血小板减少性紫癜发病机制研究进展

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,其发病机制目前仍未完全明确.慢性ITP病情易反复,部分难治性ITP预后差.近年来,对ITP发病机制的研究取得了一系列重要进展.在体液免疫机制方面,对自身抗体产生的研究有了明显进展,并提出了由自身抗体介导引起的巨核细胞数量和质量异常;在细胞免疫机制方面,除了共刺激信号理论和Th细胞失衡及一系列细胞因子异常外,又提出了调节性T细胞数量减少及细胞毒T细胞直接溶解血小板的新理论.现就ITP发病机制的研究进展作一综述.     

儿童特发性血小板减少性紫癜研究进展

儿童特发性血小板减少性紫癜(ITP)虽是一种常见疾病,但诊断和治疗仍有很多未能解决的问题。儿童发病有其特点起病急、自限性居多;男童发病率偏高;以严重血小板减少为主,而少见威胁生命的严重出血;临床过程大多平静,多数6个月内恢复,未恢复的患儿仍有一定自行恢复可能,因此被定义为仅有血小板减少、而其他方面健康的儿童身上发生的疾病状态。在发病机制方面已由过去简单认为血小板特异抗体吸附引起单核-巨噬系统吞噬造成血小板减少衍变到对机体免疫尤其是细胞免疫异常的认识,个体的遗传易感性也成为关注的焦点。被称为“免疫捕捉法”的血小板抗体检测方法逐步替代特异性差的血小板抗体检测法,血小板功能和幽门螺杆菌的监测及意义尚需探讨。对血小板(20~30)×109/L且无明显出血的患儿,观察和等待是最佳方法,而需要治疗时丙种球蛋白和糖皮质激素是一线治疗方法。目前新的治疗方法有大剂量地塞米松、抗CD20、血小板生成素(TPO)类似物等。由于远期效果不肯定、手术并发症及感染暴发,儿科医师对于脾切除越来越持谨慎态度。ITP患儿的社会心理情况也引起了人们重视。相信随着科学发展,儿童ITP的相关问题会逐步得到解决。     

淋巴细胞凋亡与特发性血小板减少性紫癜研究进展

特发性血小减少性紫癜(idiopathic thrombocytopenic purpura,ITP)是一种儿童常见的由于血小板破坏增多的出血性自身免疫病。目前，虽然许多学者在体液免疫、细胞免疫、血小板功能及内分泌等多方面进行了深入的探讨，但该病的发病机制仍然未完全明了。年近来，由于分子生物学、分子免疫学、细胞生物学等技术的飞速发展，细胞调亡成为ITP发病机制     

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。     

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患儿T细胞免疫功能研究

为探讨T淋巴细胞亚群和Th1/Th2相关细胞因子在儿童特发性血小板减少性紫癜 (ITP)中变化及应用肾上腺皮质激素治疗对其的影响。用PMA、Ionomycin作刺激剂 ,刺激全血中淋巴细胞表达细胞因子 ,以Mon ensin阻断细胞因子分泌至胞外 ,应用两种免疫荧光抗体同时标记淋巴细胞的膜表面特异分子和表达被阻滞在细胞内的细胞因子 ,用流式细胞仪进行检测和分析。结果 :ITP患儿外周血CD4 +细胞降低 ,CD8 +细胞升高 ,CD4 +/CD8 +降低尤为显著。治疗前Th1细胞占(20.66±2.82) %,Th2细胞占 (4.55±2.33) % ,Th1/Th2比值为4.78±0.66,明显高于正常儿童的1.43±0.19(P<0.005),治疗后与正常儿童无差异。提示ITP患儿T淋巴细胞亚群表达及比例失调 ,IFN_γ产生增多 ,TL_4产生减少 ,Th1/Th2功能异常 ;ITP是一种Th1占优势的疾病 ;肾上腺皮质激素治疗ITP能有效缓解病情     

急性特发性血小板减少性紫癜患儿外周血T细胞蛋白激酶C活性的分析

目的探讨急性特发性血小板减少性紫癜(acuteidiopathicthrombocytopenicpurpura,AITP)患儿外周血T细胞蛋白激酶C(proteinkinaseC,PKC)的活性变化及其与T细胞活化和血小板减少程度之间的关系。方法无菌采集35例急性ITP患儿及30例正常儿童外周抗凝血,用T淋巴细胞分离富集柱法分离纯化T细胞,分别用非同位素标记法检测T细胞PKC的活性变化,用流式细胞仪检测T细胞活化标志FasL蛋白的表达,血细胞计数仪计数血小板。结果急性ITP患儿T细胞PKC的总活性与正常儿童相比明显增强[(0.97±0.21)nmol/(min.ml)、(0.55±0.13)nmol/(min.ml),P<0.01],T细胞活化标志FasL蛋白表达与正常儿童比较显著升高[ThFasL:(32.7±3.4)%、(14.7±4.2)%;TcFasL:(17.3±9.7)%、(11.6±8.5)%,P<0.01],并且T细胞PKC的活性变化与ThFasL、TcFasL的表达均呈显著正相关(r1=0.68,r2=0.53,P<0.05),与血小板计数呈显著负相关(r=-0.75,P<0.05)。结论急性ITP患儿外周血PKC活性增强可引起患儿T细胞的活化,活性T细胞增多可导致患儿血小板大量损伤,并引起临床症状,提示PKC信号传导在急性ITP的免疫病理机制中发挥重要作用。     

特发性血小板减少性紫癜病因学研究进展

ITP是一种自身免疫性疾病，与多种因素所致的患者血小板损伤有关。其具体发病机理不完全明了，目前认为，可能与机体免疫功能失调、血小板相关抗体产生、免疫细胞介导的血小板凋亡等有关。研究表明，病毒感染、细菌感染、药物、疫苗、器官移植及造血干细胞移植、细胞凋亡、免疫分子等多种因素可能是ITP发生的病因。     

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)是儿童最常见的出血性疾病,发病率高,对儿童健康造成很大威胁.传统治疗以糖皮质激素、静脉免疫球蛋白、免疫抑制剂等非特异性手段为主,但约有1/3患儿对治疗无效,成为难治性ITP.近年来随着对ITP自身免疫发病机制的深人探讨,许多定向免疫于预措施进入临床研究,该文就儿童难治性ITP分级治疗原则、传统疗法、定向免疫干预治疗等方面的进展作一综述.     

儿童特发性血小板减少性紫癜治疗进展

特发性血小板减少性紫癜(ITP)是儿童期常见的一种免疫介导的血小板减少所的致出血性疾患.该文总结了近年来有关ITP国内外治疗进展,并比较各种药物的优缺点和切脾治疗有效性的预测方法,以期促进对ITP治疗的认识和进一步研究.     

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。     

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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。     

Management of idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura is not an uncommon bleeding disorder with a prevalence of 40–80 per million children per year. Over the last six decades, the subject of ITP has attracted the attention of pediatricians and hematologists. It is one of the subjects which has many controversies because of its unpredictable course heralded by remission relapses, and chronicity with mortality in less than 1% of cases. In the present review only the controversies in the management of acute and chronic ITP have been reviewed as it interests most pediatricians. Management of intracranial hemorrhage (ICH), severe gastrointestinal hemorrhage and menorrhagia continues to still remain a challenge in spite of newer therapies.     

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.     

Severe bleeding in idiopathic thrombocytopenic purpura

Immune thrombocytopenia in childhood is usually an acute self-limiting disorder and despite very low platelet counts is rarely complicated by serious bleeding. Several surveys indicate that only 5% or fewer children experience serious bleeding, most commonly from the nose or gastrointestinal tract. Such children need urgent measures to control bleeding, both transfusion where necessary and pharmacotherapy to raise the platelet count. Not infrequently the response of the count is less than optimal. While intracranial hemorrhage is the most feared and serious complication, it is rare, occurring in about 0.3% of cases, and if treated promptly usually has a good outcome. Treatment prior to intracranial hemorrhage does not necessarily prevent it, and it may occur after many months of otherwise clinically mild disease. The relative risk increases with the length of time a child has a very low platelet count. An international registry will help to collect more information about these important cases. Menstrual bleeding can cause severe problems for adolescents and may need a multidisciplinary approach with hormonal manipulation of the menstrual cycle.