华法林联合阿司匹林治疗对川崎病合并巨大冠状动脉瘤预后的影响

Warfarin and aspirin combination therapy for giant coronary artery aneurysm secondary to Kawasaki disease

目的探索华法林联合阿司匹林治疗对KD合并巨大冠状动脉瘤（GCAA）预后的影响，为改善KD合并GCAA患儿的预后提供临床依据。方法选取1998年1月至2012年8月首都医科大学附属北京儿童医院超声心动图诊断为KD合并GCAA的患儿65例。将患儿分为华法林＋阿司匹林组及阿司匹林组。华法林＋阿司匹林组采用小剂量阿司匹林联合华法林的治疗方案，阿司匹林组采用小剂量阿司匹林治疗方案，但不使用华法林。入组患儿分别于急性期出院后2周、1个月、3个月、6个月、1年复诊，1年以后每6个月复诊1次。随访其临床表现、冠状动脉瘤恢复情况及并发症发生情况。结果（1）KD合并GCAA患儿的发病年龄最小为3个月，最大为13岁3个月，其中≤1岁的小婴儿和／〉5岁的儿童所占比例较高，均为23．1％。（2）2组患儿冠状动脉各分支的GCAA分布情况一致。GCAA最常累及右冠状动脉，其次为左冠状动脉前降支，再次为左冠状动脉主干，较少累及左冠状动脉回旋支。（3）华法林＋阿司匹林组有17例（53．1％）出现回缩趋势，阿司匹林组为5例（41．7％）。华法林＋阿司匹林组有15例（46．9％）患儿的冠状动脉瘤内径无明显变化，阿司匹林组为7例（58．3％）。（4）华法林＋阿司匹林组有2例（6．3％）发生冠状动脉内血栓，阿司匹林组为3例（25，O％）。华法林＋阿司匹林组有1例（3．1％）发生心肌梗死，阿司匹林组为3例（25．0％）。阿司匹林组有2例（16．7％）死亡，而华法林＋阿司匹林组无死亡病例。阿司匹林组有2例（16．7％）发生冠状动脉狭窄，1例（3．1％）发生冠状动脉闭塞，华法林＋阿司匹林组有1例发生冠状动脉狭窄，但未出现冠状动脉闭塞。（5）华法林＋阿司匹林组有1例发生严重出血事件，为蛛网膜下腔出血。另外，有8例出现鼻出血，共19例次。阿司匹林组无严重出血事件发生，仅有3例次出现少量鼻出血。结论华法林联合小剂量阿司匹林在KD合并GCAA患儿的长期抗凝过程中虽然对于GCAA的回缩率无明显影响，但可以有效降低血栓形成、心肌梗死、猝死等并发症的发生率。华法林的应用过程中易发生出血事件，应定期监测凝血功能，并根据临床实际情况调节药物用量。

Objective To explore whether the warfarin and aspirin combination therapy can prevent cardiovascular events in patients with giant coronary artery aneurysm （GCAA） caused by Kawasaki disease （KD）. Methods Children who had been diagnosed as GCAA secondary to KD in Beijing Children＇s Hospital Affiliated to Capital Medical University between Jan. 1998 and Aug. 2012 were enrolled in this study. They were divided into the warfarin plus aspirin group （ combination group） and aspirin group. The combination group used the therapy of warfarin and small dose aspirin in the long-term anticoagulation treatment, while the aspirin group used small dosage of aspirin without warfarin. Both groups were followed at the time points of 2^nd week, 1^st month ,3^rd month,6^th month, and 1^st year after discharge of the acute stage. Then these children were followed every 6 months. Data on each followed-up included clinical manifestations, coronary artery aneurysm recovery situation and complications. Results （ 1 ） The onset age of GCAA caused by KD ranged from 3 months to 13 years and 3 months. Infants who were ≤ 1 year old and children who were ≥5 years old were more susceptible to this disease, their proportion were both 23.1% . （2） The distribution of GCAA in both groups were similar. GCAA most commonly occurred in the right coronary artery, then the left anterior descending coronary artery, and then the main trunk of left coronary artery, the left circumflex artery was rarely affected. （ 3 ） Coronary artery aneurysm in 17 cases（53.1% ） retracted in the warfarin combined with aspirin group,while 5 cases（41.7% ） in the aspirin group. Fifteen cases（46.9% ） in the combination group hadn＇t obvious change ,while the aspirin group got 7 cases（58.3% ）. （4）During the follow-up,2 children（6.3% ）complicated with intracoronary thromboses in the combination group,while 3 cases（25.0% ） in the aspirin group. One case（3.1% ） in the combination group suffered myocardi al infarction,while 3 eases（25.0% ） in the asprin group. Two cases （ 16.7% ） in the aspirin group died, while none in the combination group. Coronary artery stenosis occurred in 2 cases （16.7%） in the aspirin group, while 1 case （3. 1% ） in the combination group. One child had coronary artery occlusion in the aspirin group, while none in the combination group. （5） The combination group had 1 case of serious bleeding event, subarachnoid hemorrhage. In addition, there were 8 cases of nasal bleeding,a total of 19 person-time. There was no serious bleeding event in the aspirin group,only 3 person-time small mount of nasal bleeding. Conclusions Althought warfarin plus aspirin therapy for the long-term anticoagulation treatment in GCAA caused by KD can not affect the retraction of GCAA,it may decrease the incidence of thrombosis, myocardial infarction and mortality. Bleeding complication is more common during the application of wa- farin. Therefore the dose of warfarin should be tailored in various children according to the clinical situation,and bleeding complication should be monitored.