华法林联合阿司匹林治疗川崎病并多发中型及巨大型冠状动脉瘤临床研究

Clinical study of Warfarin combined with Aspirin in the treatment of Kawasaki disease complicated with multiple medium and giant coronary artery aneurysms

目的探讨华法林联合阿司匹林治疗川崎病(KD)并多发中型及巨大冠状动脉瘤的安全性和有效性。方法收集2014年4月至2018年12月在广州市妇女儿童医疗中心确诊为KD并多发中型冠状动脉瘤及巨大冠状动脉瘤45例患儿的临床及随访资料。31例患儿规律口服华法林联合阿司匹林治疗(试验组);14例患儿规律口服阿司匹林联合氯吡格雷治疗(对照组)。分析2组患儿一般情况、实验室检查、心电图、超声心动图、转归情况及出血并发症等。结果(1)试验组中有22例患儿超声心动图检查发现冠状动脉内有血栓形成,治疗后10例血栓消失,5例血栓减少,仅2例血栓增加。对照组5例患儿冠状动脉内有血栓形成,治疗后2例血栓减少,3例新增血栓形成;试验组患儿新增血栓数目较对照组少,增加例数较对照组少,差异有统计学意义(χ^2=6.454,P<0.05)。(2)试验组较对照组新增多发中型及巨大冠状动脉瘤例数增加缓慢[12.90%(4/31例)比14.28%(2/14例)]。(3)试验组较对照组巨大冠状动脉瘤数目下降快速[23.91%(11/46个)比10.00%(1/10个)]。(4)试验组较对照组瘤体回缩比例多[74.19%(23/31例)比42.85%(6/14例)]。(5)2组患儿在随访中血磷酸激酶同工酶及肌钙蛋白、心电图未见异常,超声心动图均未见心室扩大、室壁运动异常,均无活动性出血,无死亡病例。结论华法林联合阿司匹林治疗KD并冠状动脉瘤较安全,可有效减少血栓形成。与口服阿司匹林和氯吡格雷比较,华法林联合阿司匹林治疗可使多发中型及巨大冠状动脉瘤数目减少更多,冠状动脉瘤内径回缩比例增加。

Objective To investigate the safety and efficacy of Warfarin combined with Aspirin in the treatment of multiple medium and giant coronary artery aneurysms in Kawasaki disease(KD).Methods Clinical and follow-up data of 45 children diagnosed with KD complicated with multiple medium-sized and giant coronary artery aneurysms from April 2014 to December 2018 at Guangzhou Women and Children′s Medical Center were collected.These children were divided into 2 groups.A total of 31 cases received regular oral Warfarin combined with Aspirin called experimental group.There were 14 patients treated with oral Aspirin and Clopidogrel called control group.General information,laboratory examination,electrocardiogram,echocardiography,outcome and bleeding complications of the 2 groups were analyzed retrospectively.Results(1)In experimental group,there were 22 patients found thrombosis under echocardiography.The 10 patients′thrombosis disappeared,5 patients′thrombosis reduced,and 2 patients′increased after treatment.In control group,there were 5 cases found thrombosis.The 2 cases′thrombosis reduced and 3 cases′throm-bosis increased.The number of thrombosis in experimental group was significantly reduced,and the number of new thrombosis was less than that in control group(χ^2=6.454,P<0.05).(2)The number of coronary artery aneurysms in experimental group increased slowly than that in control group[12.90%(4/31 cases)vs.14.28%(2/14 cases)].(3)The number of coronary artery aneurysms in experimental group decreased rapidly than that in control group[23.91%(11/46 cases)vs.10.00%(1/10 cases)].(4)The number of cases of tumor retraction in experimental group was more than that in control group[74.19%(23/31 cases)vs.42.85%(6/14 cases)].(5)During the followed-up,there was no abnormality in the blood phosphokinase isozyme and troponin,no abnormality in the electrocardiogram and echocardiogram,no ventricular enlargement and abnormal ventricular wall movement,and the ejection fraction value was within the normal range.No active bleeding and no death occurred in the two groups.Conclusions Warfarin combined with Aspirin is very safe and effective in the treatment of KD coronary tumor,it can reduce thrombosis effectively.Compared with oral Aspirin and Clopidogrel,Warfarin combined with Aspirin can reduce the number of multiple medium-sized and large coronary artery aneurysms and reduce the diameter of coronary artery aneurysms.