摘要
目的探讨根据炎症指标和血栓标志物恢复正常的时间及超声心动图检查结果,而停止低剂量阿司匹林治疗,对川崎病疗效及预后的影响。方法选择2013年6月至2017年12月,于首都儿科研究所附属儿童医院住院治疗的82例川崎病患儿为研究对象。根据川崎病类型,将82例患儿分为完全川崎病(CKD)组(n=48)及不完全川崎病(IKD)组(n=34)。此外,根据出院时超声心动图检查结果是否伴冠状动脉病变(CAL),将82例患儿分为CAL组(n=9)及无CAL组(n=73)。对所有患儿于急性期治疗后发热消退达72h时,开始采取低剂量阿司匹林口服治疗,剂量为3～5mg/(kg·d)。在出院后8周的随访期内,监测患儿炎症指标红细胞沉降率(ESR)及C反应蛋白(CRP),以及血栓标志物血小板及D-二聚体水平;当4项指标均正常,并且超声心动图未发现合并CAL时,停止低剂量阿司匹林治疗,并继续随访至患儿出院后8周。采用t检验、Wilcoxon秩和检验及χ~2检验,对如下计量与计数资料进行统计学比较。(1)CKD组与IKD组、CAL组与无CAL组患儿的入院时临床资料,以及治疗后炎症指标和血栓标志物恢复正常的时间比较;(2)不同分类情况下,这82例川崎病患儿炎症指标恢复正常的时间比较。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》的要求。结果 (1)本研究川崎病患儿入院时,血清CRP及D-二聚体水平比较:CKD组[(10.2±4.9)mg/L,(1.1±0.3)mg/L]高于IKD组[(7.4±3.9)mg/L,(0.9±0.5)mg/L],CAL组[(13.9±7.6)mg/L,(1.7±1.5)mg/L]高于无CAL组[(8.5±3.9)mg/L,(1.0±0.7)mg/L],并且差异均有统计学意义(t=2.638,P=0.007;t=2.716,P=0.027;t=3.402,P=0.001;t=0.382,P=0.017);入院时血清白蛋白水平比较:CKD组[(35.5±4.3)g/L]低于IKD组[(37.5±3.6)g/L],CAL组[(32.3±3.5)g/L]低于无CAL组[(36.4±3.8)g/L],并且差异均有统计学意义(t=2.324,P=0.016;t=4.170,P<0.001)。(2)CKD组与IKD组、CAL组与无CAL组患儿中,男性患儿比例,入院时Harada评分、白细胞计数、血红蛋白(Hb)值、血细胞比容(HCT)、血小板计数、红细胞沉降率(ESR)、天冬氨酸氨基转移酶(AST)水平、丙氨酸转氨酶(ALT)水平,以及治疗后ESR、CRP、血小板计数、D-二聚体水平恢复正常的时间比较,差异均无统计学意义(P>0.05)。(3)本研究82例川崎病患儿治疗后,炎症指标及血栓标志物恢复正常的时间,ESR为(44.2±9.4)d,CRP为(14.4±5.5)d,血小板计数为(31.5±10.9)d,D-二聚体水平为(33.5±6.3)d。(4)本研究川崎病患儿中,男性患儿ESR及CRP恢复正常的时间[(46.3±5.2)d,(16.4±5.6)d],均长于女性患儿的[(43.4±5.0)d,(13.3±4.8)d],并且差异均有统计学意义(t=2.106,P=0.012;t=2.308,P=0.010);而发热持续时间≥7d和<7d,对静脉注射免疫球蛋白(IVIG)有反应和无反应,以及Harada评分≥4分和<4分情况下的ESR及CRP恢复正常的时间比较,差异均无统计学意义(P>0.05)。(5)本研究川崎病患儿中,出院时伴CAL的1例CKD患儿和其余73例无CAL患儿,均在出院后3～4周时,复查炎症指标及血栓标志物水平正常,并且超声心动图提示无CAL后,终止低剂量阿司匹林治疗,并在之后的随访期内,无新的CAL发生。结论通过对炎症指标和血栓标志物水平的监控,结合超声心动图检查结果,可个体化调整川崎病急性期后低剂量阿司匹林的使用时间,而不影响临床疗效及预后。
Objective To investigate the effect of discontinuing low dose aspirin treatment on the efficacy and prognosis of Kawasaki disease based on normalization time of inflammation indexes and thrombus markers,and echocardiography results.Methods From June 2013 to December 2017,a total of 82 children with Kawasaki disease who were hospitalized at the Children′s Hospital of Capital Institute of Pediatrics were chosen as research objects.According to the type of Kawasaki disease,82 children were divided into complete Kawasaki disease(CKD)group(n=48)and incomplete Kawasaki disease(IKD)group(n=34).In addition,82 children were also divided into coronary artery lesion(CAL)group(n=9)and none CAL group(n=73)according to whether complicated with CAL of the results of echocardiography at discharge from hospital.Low dose aspirin with 3-5 mg/(kg·d)by oral were given to all patients at the time point of 72 h of normal body temperature after acute phase treatment.During 8 weeks of follow up period after discharge from hospital,the erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)of inflammation indexes,as well as platelet and D-dimer levels of thrombus markers were monitored;when all these four indicators were normalized and CAL were not found by echocardiography,low dose aspirin were discontinued and still continued follow up until 8 weeks after discharge.Statistical analysis was performed on the following measurement and numeration data using t test,Wilcoxon rank sum test and chi-square test.①Clinical data at admission,as well as normalization time of inflammatory indexes and thrombus markers after treatment between CKD group and IKD group,also between CAL group and none CAL group of children.②Normalization time of inflammatory indexes of 82 cases of Kawasaki disease children among different conditions.This study was in line with World Medical Association Declaration of Helsinki revised in 2013.Results①Comparison of serum CRP and D-dimer levels in children with Kawasaki disease at admission:CRP and D-dimer levels were(10.2±4.9)mg/L and(1.1±0.3)mg/L,respectively in CKD group,which were higher than IKD group′s(7.4±3.9)mg/L and(0.9±0.5)mg/L;and those two indexes in CAL group were(13.9±7.6)mg/L and(1.7±1.5)mg/L,respectively,which were higher than none CAL group′s(8.5±3.9)mg/L and(1.0±0.7)mg/L,and all the differences above were statistically significant(t=2.638,P=0.007;t=2.716,P=0.027;t=3.402,P=0.001;t=0.382,P=0.017).Comparison of serum albumin levels in children with Kawasaki disease at admission:serum albumin level was(35.5±4.3)g/L in CKD group,which was lower than IKD group′s(37.5±3.6)g/L;and this index was(32.3±3.5)g/L in CAL group,which was lower than none CAL group′s(36.4±3.8)g/L,and the differences were statistically significant(t=2.324,P=0.016;t=4.170,P<0.001).②There were no significant differences between CKD group and IKD group,or between CAL group and none CAL group in ratio of males,Harada scores,white blood cell count,hemoglobin(Hb)value,hematocrit(HCT),blood platelet count,erythrocyte sedimentation rate(ESR),aspartate aminotransferase(AST)and alanine transarninase(ALT)levels at admission,also normalization time of ESR,CRP,blood platelet count and D-dimer level after treatment(P>0.05).③The normalization times of inflammatory indexes and thrombus markers in 82 children with Kawasaki disease after treatment were(44.2±9.4)d of ESR,(14.4±5.5)d of CRP,(31.5±10.9)d of blood platelet count and(33.5±6.3)d of D-dimer level.④The normalization time of ESR and CRP in male children with Kawasaki disease of this study were(46.3±5.2)d and(16.4±5.6)d,respectively,which were longer than female children′s(43.4±5.0)d and(13.3±4.8)d,and the differences were statistically significant(t=2.106,P=0.012;t=2.308,P=0.010).There were no significant differences under the condition between the persistent of fever≥7 d and<7 d,between response to and no response to intravenous immunoglobulin(IVIG),betweem Harada score≥4 and<4 in normalization time of ESR and CRP(P>0.05).⑤One CKD child complicated with CAL and the other 73 children without CAL at the time of discharge had normalized levels of inflammatory indexes and thrombus markers after 3-4 weeks of discharge,also no CAL by echocardiography.Therefore,low dose aspirin treatment was discontinued for these children,and no new CAL occurred during the follow up period.Conclusions By monitoring the levels of inflammatory indexes and thrombus markers,and with echocardiography,low dose aspirin treatment after acute phase of Kawasaki disease can be adjusted individually without affecting clinical efficacy and prognosis.
作者
丛晓辉
阿依布拉克.阿布都艾尼
鲁方圆
石琳
Cong Xiaohui;Ayibulake·Abuduaini;Lu Fangyuan;Shi Lin(Department of Cardiovascular,Children′s Hospital,Capital Institute of Pediatrics,Beijing 100020,China;Department of Pediatrics,Hotan Prefecture People′s Hospital of Xinjiang Uygur Autonomous Region,Hotan 848000,Xinjiang Uygur Autonomous Region,China)
出处
《中华妇幼临床医学杂志（电子版）》
CAS
2018年第6期691-697,共7页
Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)
基金
"十二五"国家科技支撑计划项目(2012BAI03B03)~~
