【作者】 王娟娟；

【导师】 严文华；

【作者基本信息】 苏州大学 ， 儿科学， 2021， 硕士

【摘要】 目的:回顾性分析314例住院川崎病(Kawasaki disease,KD)患儿临床特点,分析KD并发冠状动脉病变(Coronary artery lesion,CAL)的相关因素,分析氯吡格雷用于KD急性期的疗效,探讨氯吡格雷在川崎病抗血小板治疗的临床价值。方法:(1)收集2019年4月～2021年5月在苏州大学附属儿童医院心血管内科住院确诊为川崎病(KD)的314例的临床资料,(2)采用经体表面积校正Z值判断冠状动脉病变损伤情况,对314例川崎病结合超声心动图检查结果,分为冠状动脉病变(CAL)组和无冠状动脉病变(Non-coronary artery lesion,NCAL)组,探讨KD并发冠状动脉病变(Coronary artery lesion,CAL)的相关因素,进行统计学分析,(3)分析利用外周血细胞参数如中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)预测川崎病伴冠状动脉病变的临床价值,(4)回顾分析并比较仅用阿司匹林药抗血小板(单一组)、阿司匹林联用双密达莫抗血小板(双密达莫组)及阿司匹林联用氯吡格雷强化抗血小板(氯吡格雷组)诊治川崎病冠脉扩张的疗效。结果:一、314例KD临床特点的分析:1、基本资料分析1.1 314例KD基本情况:(1)性别:男200例,女114例,男、女比例为1.75:1;(2)年龄:54天～13岁,≤6月组23例(7.3%),～3岁组182例(57.9%),≥3岁组109例(34.7%);(3)KD的分类:①完全KD 307例(97.7%),不完全KD 7例(2.2%),②IVIG 敏感性 KD 298 例(94.9%),IVIG 无反应 KD 16 例(5.1%),③CAL发生率34.7%(109/314例),其中仅冠状动脉扩张72例,小型冠状动脉瘤33例,中型冠状动脉瘤3例,巨大冠状动脉瘤1例。1.2冠脉损害情况分析:1.2.1 CAL组与NCAL组相比较,男性患儿CAL发生率高,差异有统计学意义(P<0.05)。1.2.2 CAL组与NCAL组临床表现相比较,口唇改变发生率CAL组低于NCAL组,差异有统计学意义(P<0.05)。1.2.3实验室检测指标比较,CAL组患儿中性粒细胞计数/淋巴细胞计数比值(NLR)、CRP、肌钙蛋白高于NCAL组,白蛋白水平低于NCAL组,差异有统计学意义(均P<0.05)。1.2.4 采用受试者工作特征曲线(Receiver operating characteristic curveROC)曲线,预测KD并发CAL的CRP的截断值为36.495mg/L,灵敏度和特异性分别为86.2%和66.2%。预测KD并发CAL的NLR的截断值为4.225,灵敏度和特异性分别为38.5%和 20%。1.2.5Logistic回归分析,结果提示男性、白蛋白降低、CRP、NLR、肌钙蛋白升高为KD并发CAL的危险因素。1.3.抗血小板聚集药使用分析1.3.1回顾分析314例川崎病患儿,按照其抗血小板用药分为单用阿司匹林组183例、使用阿司匹林+双密达莫组59例及使用阿司匹林+氯吡格雷组72例。1.3.2三个组用药治疗CAL前后血常规比较,治疗后WBC计数、NLR 比值均下降,差异有明显统计学意义(P<0.05)。组间比较还发现单用阿司匹林组、阿司匹林+双嘧达莫组PLT计数治疗后上升,有统计学意义(P<0.05),推测氯吡格雷可能抑制PLT计数上升。1.3.3三个组用药治疗NCAL前后血常规比较,治疗后WBC计数、NLR 比值均下降,差异有明显统计学意义(P<0.05)。组间比较还发现阿司匹林组、阿司匹林+双嘧达莫组PLT计数治疗后上升,而氯吡格雷组治疗后血小板计数下降,认为氯吡格雷具有更强的抗血小板作用。结论:1、男性、白蛋白降低、肌钙蛋白升高、C反应蛋白增高是KD并发CAL的危险因素。2、中性粒细胞计数/淋巴细胞计数比值达4.225、C反应蛋白增高达36.495mg/L是预测KD并发CAL的较好检测指标。3、在使用阿司匹林及静脉滴注人免疫球蛋白治疗川崎病基础上,氯吡格雷具有更佳的抗血小板作用。目的:采用心脏超声检查随访38例KD并发冠状动脉瘤(Coronary artery aneurysms,CAA)的患儿恢复情况;在随访过程中,观察氯吡格雷在KD合并CAA患儿的疗效作用,评价冠状动脉瘤(CAA)早中期预后。方法:(1)收集2015年01月-2019年12月在苏州大学附属儿童医院诊断及随访的川崎病合并中型冠状动脉瘤及巨大冠状动脉瘤38例的患儿病历资料,收集诊断及随访期间性别、年龄、身高和体重、药物治疗、随访心脏彩超冠状动脉内径的数据,(2)结合双联抗血小板诊治(阿司匹林、氯吡格雷),将随访的冠状动脉瘤病人分为应用氯吡格雷组与未使用氯吡格雷组,采用心超检查来评价冠状动脉瘤演变情况及冠状动脉内径变化,评价川崎病合并CAA早中期预后。结果:一.随访冠状动脉瘤患儿基本资料分析:2.1.1截至本研究终点(1)38例CAA患儿中2例(5.3%)仅随访1次,余36例纳入本研究,平均随访时间14月(3月,39月),纳入患儿全部完成随访3次,(2)36例患儿中男27例(75%)、女9例(25%),男女比例为3:1,(3)患病年龄2.4(1.1～4.4)岁,(4)入组36例CAA患儿,其中中型冠状动脉瘤30例(83%),巨型冠状动脉瘤6例(17%),(5)所有患儿都无家族遗传史。2.1.2冠状动脉瘤瘤体病初时分布情况,CAA组中病变血管共计144支,瘤体的直径范围4～19.2mm,总共有57支血管形成冠状动脉瘤,其中冠状动脉瘤最易发生于右侧冠脉主干及近端,其次为左前降支。36例CAA患儿中18例(50%)仅累及单支冠状动脉,6例(27.8%)累及2支冠状动脉,3例(16.7%)累及3支冠状动脉,2例(5.6%)累及4支冠状动脉。二.应用氯吡格雷时冠状动脉瘤回缩分析2.2.1收集36例CAA患儿抗血小板用药情况,其中使用氯吡格雷组27例(75%)、未使用氯吡格雷组9例(25%)。氯吡格雷组中44支血管受累,21支(47.7%)血管回缩、8支(18.2%)血管无明显变化、15支(34.1%)部分缩小。未使用氯吡格雷组中14支血管受累,4支(28.6%)血管回缩、7支(50%)血管无明显变化、3支(21.4%)部分缩小。2.2.2对两组药物治疗后不同部位冠状动脉恢复情况进行分析,氯吡格雷组不同位置的CAA内径均有不同程度回缩趋势(P<0.05),未使用氯吡格雷组不同位置CAA内径稍有回缩,但差异无统计意义(P>0.05)。2.2.3巨型冠状动脉瘤内径恢复情况:巨型冠状动脉瘤共6例,其中氯吡格雷组5例,未使用氯吡格雷组1例。氯吡格雷组累及左冠脉主干1支,随访前内径9.4mm,随访后回缩至2.3mm;累及左前降支5支,随访前内径11.78±4.22mm,随访后内径8.42±3.57mm,差异有统计学意义(t=3.033,P=0.039);未累及左回旋支;累及右主干近段5支,随访前内径9.70±0.51mm,随访后内径7.30±2.99mm,内径较前回缩,但差异无统计学意义(t=1.854,P=0.137)。未使用氯吡格雷组1例,累及左前降支1例,随访前内径8.3mm,随访后内径8.0mm,内径无明显回缩。结论:川崎病合并CAA以右冠状动脉主干及近端、左冠状动脉前降支最为常见。川崎病合并CAA患儿使用氯吡格雷可促进瘤体的回缩,对促进冠状动脉瘤恢复有一定作用。更多还原

【Abstract】 Objective:To retrospectively analyze the clinical characteristics of 314 hospitalized children with Kawasaki disease(Kawasaki disease,KD),analyze the related factors of KD complicated by coronary artery lesion(CAL).To explore the clinical value of clopidogrel in antiplatelet therapy of Kawasaki disease.Methods:(1)Collect clinical data of 314 cases of KD who were hospitalized in the Department of Cardiology,Children’s Hospital of Soochow University from April 2019 to May 2021.(2)The Z value adjusted by body surface area was used to judge coronary artery disease Injury.314 cases of Kawasaki disease combined with echocardiographic examination results were divided into CAL and NCAL group,to explore the related factors of CAL.(3)To predict CAL of KD with peripheral blood cell parameters,such as NLR.(4)Analyze and compare the evaluation of the efficacy of clopidogrel in antiplatelet therapy of Kawasaki disease.Results:1.Analysis of the clinical characteristics of 314 cases of KD:1.cilnical data1.1 314 cases of KD:(1)Gender:200 males,114 females,the ratio of male to female is 1.75:1;(2)Age:54 days to 13 years old,among them,23 cases(7.3%)≤6 months,109 cases(34.7%)≥ 3 years old;(3)KD classification:①complete KD 307 cases(97.7%),incomplete KD 7 cases(2.2%),②IVIG sensitivity KD 298 cases(94.9%),IVIG unresponsive KD 16 cases(5.1%),③the incidence of CAL accounted for 34.7%(109/314 cases),of which only 72 cases of coronary artery dilation,33 cases of small coronary aneurysms,and 3 cases of medium coronary aneurysms,only 1 case of giant coronary aneurysm.1.2 Analysis of coronary artery damage:1.2.1 Compared with the NCAL group,the incidence of CAL in male children was higher and the difference was statistically significant(P<0.05).1.2.2 Compared with the NCAL group,the incidence of lip changes in the CAL group was lower and the difference was statistically significant(P<0.05).1.2.3 The NLR、CRP and troponin of children in the CAL group were higher than those in the NCAL group,but the albumin level was lower.The difference was statistically significant(P<0.05).1.2.4 Using the receiver operating characteristic curve(ROC),the cut-off value of CRP predicted for KD with CAL is 36.495mg/L.The sensitivity is 86.2%and the specificity is 66.2%.The cut-off value of NLR for predicting KD with CAL is 4.225.The sensitivity is 38.5%and the specificity is 20%.1.2.5 Logistic regression analysis showed that male、decreased albumin and increased CRP、NLR&troponin are risk factors for KD with CAL.1.3.Analysis of the use of anti-platelet aggregation drugs1.3.1 Retrospectively analyze 314 children with KD,183 cases only take aspirin,59 cases take aspirin and double medidamole,the left 72 cases take aspirin and clopidogrel.Observe whether the coronary artery is dilated,the degree of dilation,and the change of platelet count.1.3.2 The WBC count and NLR ratio of the three groups decreased after treatment of KD with CAL(P<0.05).The PLT count increased significantly after treatment in aspirin group and dipyridamole group(P<0.05).It is speculated that clopidogrel may inhibit the increase of PLT count.1.3.3 The WBC count and NLR ratio of the three groups decreased significantly after treatment t of KD with NCAL(P<0.05).The PLT count of aspirin group and dipyridamole group increased after treatment,while the platelet count of clopidogrel group decreased after treatment.It is considered that the antiplatelet effect of clopidogrel is stronger.Conclusions:1.Male、ecreased albumin、increased troponin and increased CRP are risk factors for KD complicated with CAL.2.The NLR of 4.225 and the increase of CRP as high as 36.495mg/L are good indicators for predicting KD with CAL.3.On the basis of using aspirin and IVIG to treat KD,clopidogrel has a better antiplatelet effect.Objective:38 children with CAA complicated by KD were followed up by echocardiography.During the follow-up,the curative effect of clopidogrel in children with KD combined with CAA was observed,to evaluate the prognosis of CAA.Methods:(1)Collect the medical records of 38 children with Kawasaki disease combined with medium-sized coronary aneurysm and giant coronary aneurysm who were diagnosed and followed up in the Children’s Hospital of Soochow University from January 2015 to December 2019.The data of gender、age、height、weight、drug and follow-up coronary artery diameter in echocardiography were collected during diagnosis and followup.(2)Combined with dual antiplatelet diagnosis and treatment(aspirin,clopidogrel),the follow-up coronary aneurysm patients were divided into clopidogrel group and the nonclopidogrel group。Ultrasonography was used to evaluate the evolution of coronary aneurysm and the change of coronary artery diameter,and to evaluate the early and midterm prognosis of KD combined with CAA.Result:1.Follow-up analysis of basic data of children with CAA:2.1.1(1)38 children with CAA completed the follow-up,of which 2 cases(5.3%)were followed up only once,and the remaining 36 cases were included in the study.The average follow-up time was 14 months(3～39 months).(2)Among the 36 children,27 cases were male(75%)and the left 9 cases were female(25%).The ratio of male to female was 3:1.(3)Age of onset was 2.4(1.1～4.4)years.(4)36 children with CAA were enrolled,including 30 cases of medium coronary aneurysms(83%),6 cases of giant coronary aneurysms(17%),(5)All patients have no family history.2.1.2 The initial distribution of coronary aneurysms is a total of 144 blood vessels in the CAA group,with the diameter ranges from 4～19.2mm.A total of 57 blood vessels form coronary aneurysms.Among them,coronary aneurysms were most likely to occur in the main and proximal coronary artery on the right,followed by the left anterior descending branch.Among 36 children with CAA,18 cases(50%)occurred in a single coronary artery,6 cases(27.8%)occurred in 2 coronary arteries,3 cases(16.7%)occurred in 3 coronary arteries,and 2 cases(5.6%))occurred in 4 coronary arteries.2.Analysis of coronary aneurysm retraction with clopidogrel2.2.1 The antiplatelet medication of 36 children with CAA was collected,including 27cases(75%)in the clopidogrel group and 9 cases(25%)in the non-clopidogrel group.44 vessels were involved in the clopidogrel group,21 vessels(47.7%)were retracted,8 vessels(18.2%)had no significant change,and 15 vessels(34.1%)were partially reduced.14 vessels were involved in the non-clopidogrel group,4 vessels(28.6%)were retracted,7 vessels(50%)had no significant change,,and 3 vessels(21.4%)were partially reduced.2.2.2 The recovery of coronary arteries at different parts in the two groups after drug treatment was analyzed.The CAA diameters of different positions in the clopidogrel group had different degrees of retraction(P<0.05).The CAA diameters at different positions in the non-clopidogrel group slightly retracted,but the difference was not statistically significant(P>0.05).2.2.3 Diameter recovery of giant coronary aneurysms:there were 6 cases of giant coronary aneurysms,including 5 cases in the clopidogrel group and 1 case in the nonclopidogrel group.In the clopidogrel group,1 left coronary artery was involved,with an inner diameter of 9.4mm before follow-up,and then retracted to 2.3mm after follow-up;5 left anterior descending vessels were involved,with an inner diameter of 11.78 ± 4.22mm before follow-up,and an inner diameter of 8.42 ± 3.57mm after follow-up.It was statistically significant(t=3.033,P=0.039).The left circumflex branch was not involved.The proximal 5 branches of the right main trunk were involved,the inner diameter was 9.70±0.51mm before the follow-up,the inner diameter was 7.30±2.99mm after the follow-up.But the difference was not statistically significant(t=1.854,P=0.137).There was 1 case in the non-clopidogrel group,and 1 case involved the left anterior descending branch.The inner diameter was 8.3mm before the follow-up and 8.0mm after the follow-up.The inner diameter did not shrink significantly.Conclusion:Kawasaki disease combined with CAA is most common in the main trunk and proximal part of the right coronary artery and the anterior descending branch of the left coronary artery.Clopidogrel can promote aneurysm retraction in children with KD complicated with CAA,and may help the recovery of coronary aneurysm.更多还原