Exploring On The Basic Status And Influencing Factors Of Platelet Aggregation Rate Before Aspirin Initiation In Pediatric Congenital Heart Disease With High Risk Of Thrombosis

OBJECTIVE:By measuring the platelet aggregation rate before the first use of postoperative aspirin for children with congenital heart disease at high risk of thrombosis,the basic status and main influencing factors of the platelet aggregation rate in this population were explored,so as to supply a preliminary basis for the accurate evaluation of aspirin effect.METHODS:A prospective cohort study was carried out in our pediatric cardiac center.Children who were hospitalized for surgery from January 2020 to March 2021 at high risk of thromboembolism with congenital heart disease were included in this study.An informed consent was signed,and the arachidonic acid induced platelet aggregation rate(PAG-AA)was measured just before the first dose of aspirin after the operation.Thus,the basic status of PAG-AA for this population was obtained.Through the single factor and multiple factors analysis,the influencing factors was investigated.RESULTS:A total of 247 patients met the inclusion criteria and signed informed consent,including 100 females with median age of 13 months(13 days-6 years)and mean weight of 10.2±4.9 Kg.The median PAG-AA in basal state of was 20.70%(1.28%-86.49%))with 67.3%distributed under 55%and 47.9%under 20%.Patients undergoing cardiopulmonary bypass had a significantly lower basic PAG-AA than those without cardiopulmonary bypass(30.63±27.35 VS 57.91±27.58,P=0.013).While the basic PAG-AA were significantly lower when tests were done within 3 days after the cardiopulmonary bypass than those out of 3 days(25.61±25.60 VS 48.59±26.45,P=0.001).Cyanosis patients had an obvious higher basic PAG-AA than those in noncyanosis patients(39.22±27.36 VS 25.87±26.39,P=0.028).Univariate analysis implied that the influencing factors of the basal PAG-AA including CPB use,time of aspirin initiation(test time point),cyanosis and platelet count.Multivariate regression analysis indicated that only CPB use,test time point,and platelet count were the main independent influencing factors for the basal PAG-AA.Cyanosis had no significant influence.CONCLUSION:In children with congenital heart disease at high risk of thrombosis,the value of basal platelet aggregation rate fluctuated widely before postoperative aspirin initiation,while the majority is impaired.The basal PAG status was correlated with the time of aspirin initiation(test time point),and was also affected by the type of surgery(CPB used or not)and the platelets counts at the same time.These three factors are independent influencing factors for basal PAG-AA.Application of CPB,test within 3 days after surgery,and lower platelet counts are always associated with lower value of PAG-AA.The effect of CPB on PAG-AA was mainly within 3 days after operation.Cyanosis and little age had no significant effect on the basal PAG-AA.When PAG-AA is used as the basis for evaluating the effect of aspirin,it is recommended that the detection point be 3 days after the end of CPB.To establish the platelet aggregometry baseline prior to commencement of aspirin therapy,testing should be performed 3 days later following the procedure when effect of CPB is basically over.OBJECTIVE:In terms of the diversity on antiplatelet effect of aspirin and the high incidence of thrombosis at early and long-term stage for children with congenital heart disease(CHD)at high risk of thrombosis,we try to explore the correlation between low aspirin response and thrombotic events within 3 months,and also to evaluate whether the individualized antithrombotic strategy that aspirin is given based on the platelet function test is superior to the traditional fixed dose regimen.METHODS:A prospective randomized controlled study(registered NO.ChiCTR2000036446)was conducted in our Pediatric Surgery Center.All children less than 6 years old undergoing cardiac surgery with CHD and needing routine antithrombotic therapy with aspirin from April 2020 to March 2021 were enrolled into this study.Patients were randomly divided into fixed group(3mg/kg/d)and adjustment group according to aspirin dosage.In the fixed-dose group,the test of arachidonic acid-induced platelet aggregation(PAG-AA)was done only after the first 3 doses of aspirin,and aspirin was continued until 3 months after operation.In the adjustment group,PAG-A A was measured after 3 and 6 doses of aspirin,respectively.For those with PAG-AA>20%after 3 doses,aspirin was added to 6mg/kg/d from the primary dose of 3mg/kg/d;For those PAG-AA still more than 20%after 6 doses,patients were treated with clopidogrel 0.2mg/kg/d plus aspirin 6mg/kg/d.Low aspirin response was defined as PAG-AA≤20%after 3 doses of aspirin.The correlation between low aspirin response and thrombotic events within 3 months was analyzed,and the cumulative incidence of thrombotic events including death and the incidence of bleeding events within 3 months after surgery were compared respectively between the two groups.RESULTS:196 children(99 in the fixed group,97 in the adjustment group)were included in the final analysis.The median age was 13 months(12days-6 years),and the mean weight was(10.1±4.8)kg.There was no death in both groups within 3 months after operation.The overall incidence of low aspirin response was 12.2%(24/196).Thrombotic events occurred in 4 patients with low aspirin response and in 24 patients without low aspirin response.There was no significant correlation between low aspirin response and thrombotic events(r=-0.05,p=0.486).In the fixed dose group,the incidence of thrombosis was 15.2%(3 cases in the artificial tube,8 cases in the deep vein,3 cases in the pulmonary artery or pulmonary vein,and 1 case in the atrium),and the incidence of bleeding events was 3.0%(all mild);In the dose adjustment group,the incidence of thrombosis was 13.4%(3 cases in the artificial tube,6 cases in the deep vein,2 cases in the pulmonary artery or pulmonary vein,and 2 case in the atrium),and the incidence of bleeding events was 5.1%(4 mild and 1 severe).There was no significant difference in the incidence of thrombotic events and bleeding events between the two groups(P>0.05).CONCLUSION:In children with congenital heart disease at high risk of thrombosis,the incidence of low aspirin response is about 12.2%.However,there is no significant correlation between low aspirin response and thrombotic events within 3 months after operation.Comparing with the fixed dose regimen,aspirin dose adjustment strategy that based on the platelet aggregation test is not superior,as it doesn’t significantly reduce the incidence of thrombosis and bleeding events in the early 3 months.Routine platelet aggregation testing is not recommended.