Objective To evaluate the clinical efficacy and unravel the mechanism underlying dual antiplatelet therapy in the treatment of pediatric Kawasaki disease.Methods Seventy-eight children with acute Kawasaki disease were recruited and randomly divided into groups A (n =39) and B (n =39) by using random number table method.All patients in both groups were administered with high-dose aspirin and gamma globulin.After antipyretic therapy,patients in group A received aspirin combined with clopidogrel maintenance treatment and those in group B were treated with aspirin alone.The levels of thrombopoietin (TPO),IL-3,IL-6,NF-κB p65 mRNA,NF-κB p65 protein and MMP-9 were quantitatively measured and statistically compared before and 2 weeks after treatment.Before and 3 months after treatment,the blood platelet (PLT),mean platelet volume (MPV),platelet distribution width (PDW) and the effective rate of antiplatelet aggregation were detected and compared.During 3-year follow-up,the incidence of coronary artery disease was observed and the correlation between platelet parameters and the risk of coronary artery disease was analyzed in two groups.Results The levels of TPO,IL-3,IL-6,NF-κB p65 mRNA,NF-κB p65 protein and MMP-9 at 2 weeks after corresponding treatment were significantly lower than those before treatment in both groups (all P ＜0.05),whereas no statistical significance was observed between two groups (all P ＞ 0.05).At 3 months after treatment,the levels of PLT,MPV and PDW significantly lower than those before treatment in both groups (all P ＜ 0.05).The levels of PLT and MPV in group A were significantly lower than those in group B at 3 months after corresponding treatment (both P ＜ 0.05).At 6-and 12-month after treatment,the effective rate of antiplatelet aggregation in group A were 90％ and 95％,significantly higher compared with 72％ and 71％ in group B (both P ＜ 0.05).During 3-year follow-up,the incidence of coronary artery disease in group A was 8％,considerably lower than 26％ in group B (P ＜ 0.05).After treatment,both PLT and MPV were positively correlated with the risk of coronary artery disease (both P ＜ 0.05),whereas no correlation was noted between PDW and the incidence of coronary artery lesion (P ＞ 0.05).The overall incidence of adverse reactions was 10％ and 15％ in groups A and B with no statistical difference (P ＞ 0.05).Conclusion Aspirin combined with clopidogrel can effectively inhibit platelet aggregation,maintain the PLT and MPV at a low level and reduce the risk of coronary artery disease in children with Kawasaki disease.%目的 探讨双联抗血小板治疗小儿川崎病的疗效机制及远期随访.方法 选取78例急性期川崎病患儿,按随机数表法分为A组及B组,每组各39例.2组均予以大剂量阿司匹林及丙种球蛋白治疗,退热后A组应用阿司匹林联合氯吡格雷维持治疗,B组单用阿司匹林治疗.比较治疗前及治疗后2周2组患儿的血小板生成素(TPO)、IL-3、IL-6、核因子-κB(NF-κB) p65 mRNA及蛋白、基质金属蛋白酶-9 (MMP-9)水平,治疗前与治疗3个月后2组患儿的血小板计数、平均血小板体积(MPV)、血小板体积分布宽度(PDW)、抗血小板聚集有效率,并随访3年观察2组患儿的冠状动脉病变发生率,分析血小板参数与冠状动脉病变的相关性.结果 治疗后2周,2组患儿的TPO、IL-3、IL-6、NF-κB p65 mRNA及蛋白、MMP-9水平均低于同组治疗前(P均＜0.05),2组间比较差异无统计学意义(P＞0.05).治疗后3个月,2组患儿的血小板计数、MPV、PDW均低于同组治疗前(P均＜0.05),A组治疗后3个月的血小板、MPV均低于B组(P均＜0.05).治疗6、12个月时,A组患儿的抗血小板聚集有效率分别为90％、95％,均高于B组的72％、71％(P均＜0.05).随访3年期间A组的冠状动脉病变发生率为8％,低于B组的26％ (P ＜0.05).治疗后的血小板计数和MPV与冠状动脉病变的发生率均呈正相关(P均＜0.05),PDW与冠状动脉病变的发生无关(P＞0.05).治疗期间,2组患儿不良反应总发生率分别为10％和15％,组间比较差异无统计学意义(P＞0.05).结论 阿司匹林联合氯吡格雷治疗小儿川崎病可有效抑制血小板聚集,使血小板与MPV持续维持在较低水平,降低冠状动脉病变风险.
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