基于血小板聚集率检测的阿司匹林剂量调整方案在儿童先心病抗栓治疗中是否更优

Aspirin dosage adjustment based on platelet aggregation:is it superior in antithrombotic treatment for children with congenital heart disease?

目的 以高危血栓风险先心病儿童为对象,针对阿司匹林治疗反应多样性及近远期血栓发生率仍较高的问题,评价基于血小板功能检测目标导向的阿司匹林个体化抗栓治疗方案的临床效果是否优于传统固定剂量的给药方案。方法 采用前瞻随机对照注册研究(ChiCTR2000036446)。纳入阜外医院小儿外科中心自2020年4月~2021年4月所有行先心病手术并且需要术后常规应用阿司匹林抗栓治疗的6岁内患儿。所有入组患儿随机分为阿司匹林固定剂量组3 mg/(kg·d)和剂量调控组。剂量调控组在3剂和6剂阿司匹林后分别行花生四烯酸诱导的血小板聚集率(PAG-AA)检测。对3剂后PAG-AA>20%者,阿司匹林加量至6 mg/(kg·d);6剂后PAG-AA仍>20%者,联用氯吡格雷0.2 mg/(kg·d)治疗。比较两组患者术后3月包括死亡在内的累计血栓事件发生率和出血事件发生率。结果 对比阿司匹林反应低下、血栓事件与出血不良事件,两组患者数据比较无统计学差异。在接受相同剂量的阿司匹林[3 mg/(kg·d),1次/d]连续3剂后,不同个体的PAG-AA存在较大差异。剂量调控组通过增加阿司匹林剂量,延长阿司匹林使用时间与联合用药,整体阿司匹林反应性得到了改善,但与固定剂量组比较无统计学差异。两组在术后3月接受随访期间以及最终复查时均无死亡病例发生,两组阿司匹林反应低下病例的血栓事件和出血事件发生率比较无明显差别。Spearman相关性检测显示阿司匹林低反应与血栓事件无明显的相关性。结论 与固定剂量阿司匹林抗栓治疗方案相比,基于血小板聚集率检测的阿司匹林剂量个体化抗栓治疗方案并不具有优越性,并不能显著降低先天性心脏病高危血栓风险患儿术后早期3月内血栓及出血事件发生率。血栓事件与阿司匹林反应低下无明显相关性。

AIM To explore whether the individualized antithrombotic strategy of aspirin based on theplatelet function test is superior to the traditional fixed dose regimen in antithrombotic treatment forchildren with congenital heart disease (CHD). METHODS A prospective randomized controlled study(registered NO. ChiCTR2000036446) was conducted in our Pediatric Surgery Center. All CHD childrenless than 6 years old who underwent cardiac surgery and routine antithrombotic therapy with aspirin after surgery from April 2020 to April 2021 were enrolled into this study.The children patients were randomly divided into fixed group[3 mg/(kg·d)]and adjustment group according to aspirin dosage.In the adjustment group,the platelet aggregation induced by arachidonic acid(PAG-AA)was measured after 3 and 6 doses of aspirin.For those with PAG-AA>20%after 3 doses,aspirin was added to 6 mg/kg/d from the primary dose of 3 mg/(kg·d).For those PAG-AA still more than 20%after 6 doses,patients were treated with clopidogrel 0.2 mg/(kg·d)plus aspirin 6 mg/(kg·d).The cumulative incidence of thrombotic events including death and the incidence of bleeding events within 3 months after surgery was compared respectively between the two groups.RESULTS There was no statistically significant difference in the data between the two groups of patients when comparing low aspirin response,thrombotic events,and adverse bleeding events.After receiving the same dose of aspirin[3 mg/(kg·d),once a day]for three consecutive doses,there were significant differences in PAG-AA among different individuals.The dose control group improved overall aspirin responsiveness by increasing the dose of aspirin,prolonging the duration of aspirin use,and combining medication,but there was no statistically significant difference compared to the fixed dose group.There were no deaths between the two groups during the follow-up period of 3 months after surgery and at the final follow-up.There was no significant difference in the incidence of thrombotic and bleeding events between the two groups of aspirin responsive patients.Spearman correlation testing showed no significant correlation between low aspirin response and thrombotic events.CONCLUSION Compared with the fixed dose regimen,aspirin dose adjustment strategy based on the platelet aggregation test is not superior,as it does not significantly reduce the incidence of thrombosis and bleeding events in the early 3 months after surgery in CHD children at high risk of thrombosis.There is no prominent association between low aspirin response and thrombotic events.