摘要
目的 探讨儿童免疫性血小板减少症(ITP)慢性化的临床特征及影响因素.方法 280例ITP患儿据病程分为慢性ITP(cITP,病程＞12个月,n=67)组和非cITP组[含新诊断ITP(nITP,病程＜3个月,n=159)和持续性ITP(pITP,病程为3～12个月,n=54],收集2组患儿一般资料(性别、起病年龄、发病季节、发病前有无感染史、出血方式、住院日期及病程、治疗方案等),抽取外周血检测初诊和治疗后血小板计数、外周血淋巴细胞计数(ALC)及中性粒细胞绝对值,采用Luminex分析仪检测血清中血小板抗体的强度和特异性,采用间接免疫荧光法和明胶颗粒凝集法定量检测血清抗核抗体(ANA)和肺炎支原体抗体滴度,采用酶联免疫法和实时荧光定量技术检测Epstein-Barr(EB)病毒、巨细胞病毒的抗体及DNA水平;采集ITP患儿骨髓涂片,镜检计数原始、幼稚、颗粒、产板巨核细胞及裸核数目;有明显出血表现ITP患儿行激素、静注免疫球蛋白(IVIG)及激素+IVIG治疗,检测治疗1周时出血情况、血小板数、评估治疗效果;采用单因素和多因素logistic回归分析ITP患儿预后的影响因素,采用受试者工作特征(ROC)曲线下面积(AUC)评估独立影响因素对ITP慢性化的预测价值.结果 280例ITP患儿中男女比为1.28:1,诊断中位年龄为2岁9月,cITP患儿男女比为1.39∶1,慢性化率23.9％,男性与女性患儿慢性化率分别为24.8％和22.8％,组间比较差异无统计学意义(x2=0.163,P=0.686);cITP组学龄期ITP患儿慢性化率最高(48.9％);初诊血小板计数、初诊淋巴细胞绝对值(ALC)、起病年龄、前驱感染、出血方式与儿童ITP的预后相关(P＜0.05);激素+IVIG治疗的ITP患儿慢性化率最高(31.4％);影响因素分析显示,初诊ALC、起病年龄、出血方式是儿童ITP进展为慢性的独立影响因素(P＜0.05);经ROC分析,初诊ALC(最佳截点值2.52 × 109/L)、起病年龄及出血方式预测ITP慢性化的AUC分别为0.739、0.707及0.544,3者联合ROC曲线的AUC为0.769、敏感性为62.7％及特异性为80.8％.结论 ITP在幼儿期患病率高,感染是ITP在儿童时期发病的重要诱因;起病年龄、出血方式、初诊ALC可作为初次发病时判断ITP预后的指标,3者联合对cITP的预测价值更大;cITP组患儿对糖皮质激素反应低下或无反应,需要依赖于其他二线药物治疗.
Abstract
Objective To investigate the clinical features and influence factors of children with chronic immune thrombocytopenia(ITP).Methods According to the course of disease,280 children with ITP were divided into chronic ITP(cITP,course of disease＞12 months,n=67)group and non-cITP group,including newly diagnosed ITP(nITP,course of disease＜3 months,n=159)and persistent ITP(pITP,course of disease＞12 months,n=54).The clinical features(sex,onset age,onset season,infection history before onset,bleeding mode,hospitalization date and course,treatment plan,etc.)of ITP children in the two groups were collected.The peripheral blood of the patients was taken to detect the platelet count,peripheral blood lymphocyte count(ALC)and neutrophil absolute value after initial diagnosis and treatment,the strength and specificity of platelet antibody in serum were detected by Luminex analyzer,the titers of serum anti-nuclear antibody(ANA)and mycoplasma pneumoniae(MP)antibody were quantitatively detected by indirect immunofluorescence method and gelatin particle agglutination method.The antibody and DNA levels of Epstein-Barr(EB)virus and cytomegalovirus were detected by enzyme-linked immunosorbent assay and real-time fluorescence quantitative technique.Bone marrow smears of ITP children was collected,and the numbers of primitive,naive,granular,plate-producing megakaryocytes and naked nuclei were counted by microscopy.ITP Children with obvious bleeding were treated with hormone,intravenous immunoglobulin(IVIG)and hormone+IVIG therapies.The bleeding situation and platelet count of ITP children after 1 week of treatment were collected,and the therapeutic effect was evaluated.Univariate and multivariate logistic regression were used to analyze the factors affecting the prognosis.The area under receiver operating characteristic(ROC)curve(AUC)was used to evaluate the predictive value of independent influencing factors for ITP chronicity.Results Of 280 children with ITP,157 were male(56.1％),123 were female(43.9％);the male-female ratio was 1.28:1.The median age of the patients was 2 years and 9 months.The male-female ratio of cITP children was 1.39∶1,and the chronic rate was 23.9％.The chronic rates of male and female children were 24.8％and 22.8％respectively.There was no significant difference between the groups(x2=0.163,P=0.686).The chronic rate of ITP children of schoolage in cITP group was the highest(48.9％).Univariate analysis showed that platelet count and peripheral blood lymphocyte count(ALC)at first diagnosis,age of onset,preinfection,and mode of bleeding were correlated with the prognosis of children with ITP(P＜0.05).The chronic rate of ITP children treated with hormone combined with gamma globulin was the highest(31.4％).Multivariate analysis showed that ALC at first diagnosis,age of onset and mode of bleeding were independent factors influencing the progression of acute ITP to chronic one(P＜0.05).ROC showed that the AUCs of initial diagnosis ALC(optimal cut-off value 2.52 × 109/L),onset age and bleeding mode were 0.739,0.707,and 0.544,respectively.The AUC of ROC curve drawn by the combined treatment of the three was 0.769,the sensitivity was 62.7％and the specificity was 80.8％.Conclusions The prevalence of ITP is high during early childhood,infection is an important cause of ITP in children.ALC at the first diagnosis,age of onset and mode of bleeding are early predictors of chronic ITP of children.The combination of the three factors has better predictive value for chronic ITP.Children in cITP group have weak or no response to glucocorticoid and need to rely on other second-line drugs.
基金项目
国家自然科学基金(82060033)
贵州省科技计划项目(黔科合基础-zk[2023]一般366)
贵州省科技计划项目(黔科合人才平台-CXTD[2021]002)
NETL
NSTL
万方数据