| Background and purpose of researchHigh-dose prophylaxis can control bleeding effectively and protect the joint to a normal state,but it is difficult for developing countries to bear the high cost of which.Hemophiliac in developing countries can only treat with low and intermediate-dose prophylaxis and even on-demand treatment.A number of studies abroad and in China have proved preliminarily that the effect of low and intermediate-dose prophylaxis on improving the clinical bleeding phenotype and improving the quality of life is obviously better than that of the on-demand treatment,but there is no long-term observation data support.The study on low and intermediate-dose prophylaxis is mainly based on the clinical hemorrhagic phenotype like annual bleeding rate(ABR)and annual joint bleeding rate(AJBR).The clinical hemorrhagic phenotype is the observation index.In recent years,the clinical hemorrhagic phenotype has been found to be weakly related to the joint damage.There has not been a report on the effect of low and intermediate-dose prophylaxis on children with severe hemophilia A with the joint assessment layer.In this study,a comprehensive evaluation of the newly developed joint structure and functional status was used to explore the changes in the long-term follow-up observation,and to analyze the related factors to provide the basis for the revision of the guidebook for diagnosis and treatment of hemophilia in China and other developing countries.Research method1.Object of study:children with severe hemophilia A receiving factor ? for treatment between 4 to 17 years old(F?:C<2%,and ABR is more than 12 times in the condition of on-demand or without treatment)2.Grouping and classification:20 cases in the intermediate-dose prophylaxis group(15-20U/kg,2-3 times a week,and 45-60IU/kg/weeks),18 cases in the low-dose prophylaxis group(10-15U/kg,2-3 times a week,and less than 30IU/kg/weeks)and 15 cases in the on-demand treatment group.The annual bleeding times of the most serious single target joint less than 3 times was divided into class I T,and the annual bleeding times of the most serious single target joint more than 3 times was divided into class II T.The ultrasonic of bilateral elbow joint,knee joint and ankle joint are all scoreless was divided into class I B,and ultrasonic of bilateral elbow joint,knee joint and ankle joint are not all scoreless was divided into class IIB.No vigorous activities on the daily lifestyle is were divided into class I Q,and without vigorous activities on the daily lifestyle is were divided into class II Q.3.Study indicators:(1)clinical hemorrhagic phenotypes,including ABR,AJBR,ATJBR and the most serious single target joint annual bleeding rate;(2)changes in the number of target joints;(3)joint structure:ultrasound and MRI score;(4)joint function:HJHS scale;(5)activity assessment:FISH scale;(6)quality of life assessment:CHO-KLAT scale.4.Methods of statistical:statistical software IBM SPSS 22 was used for data analysis.When comparing the two sets of variables,Kruskal-Wallis and t test were used;Spearman rank was used to analyze the correlation of two indexes.Research resultsChapter one:the changes of joint structure and function in children with severe hemophilia A treated with low and intermediate-dose prophylaxis.1.General data:a median follow-up period of 359 days(about 12 months),53 cases were completed according to the plan of follow-up data collection without withdrawal cases.There was no significant difference in age,weight,body mass index,age of first bleeding,age of first bleeding,age of diagnosis,and activity of baseline factor in the three groups(P>0.05).2.The Clinical hemorrhagic phenotype and number of target:low and intermediate-dose prophylaxis groups can not achieve the goal without bleeding,but compared with the on-demand treatment group,the clinical bleeding phenotype is improved obviously(61.34%to 75.81%in the low-dose prophylaxis group and 72.39%to 84.94%in the intermediate-dose group),and there is significant statistical difference(P= 0.000-0.003).The improvement of the intermediate-dose prophylaxis group was better than the low-dose prophylaxis group(P=0.005-0.016).After 12 months of follow-up,the number of target joints could not be reduced in both low and intermediate-dose prophylaxis groups,but in the control of the increase of the number of target joints,the intermediate-dose prophylaxis group was superior to the on-demand treatment group(P=0.004)and low-dose prophylaxis.There was no significant difference between the low-dose prophylaxis group and the on-demand treatment group,the intermediate-dose prophylaxis group and the low-dose prophylaxis group(P=0.127,0.123).3.The changes of joint function and activity ability(1)The function of joint:the variation of HJHS total score in the three groups of children with hemophilia A after the 3 months,6 months,9 months and 12 months were all positive.The variation of the low and intermediate-dose prophylaxis groups were less than the on-demand treatment group(P=0.000-0.012),but there was no significant difference between the intermediate-dose prophylaxis and the low-dose prophylaxis group(P>0.05).(2)Activity ability:the variation of FISH total score of three groups of children with hemophilia A after 6 months and 12 months follow-up was negative,and the variation of low and intermediate-dose prophylaxis groups were less than that of the on-demand treatment group(P=0.000-0.020),but there was no significant difference between the intermediate-dose prophylaxis group and the low-dose prophylaxis group(P>0.05).4.Ultrasonographic structure and functional changes of the most serious single target joint(1)The ultrasound imaging structure changes of the most serious single target joint:follow up 3 months,6 months,9 months and 12 months,the variation of ultrasound score of the most serious single target joint in the three groups were positive,The three groups of children with the most serious single target joint ultrasound score changes were positive.The variation of ultrasound of the most serious single target joint in low and intermediate-dose prophylaxis groups were less than those in the on-demand treatment group.There were significant differences between,which after the follow-up of 6 months,9 months and 12 months(P =0.000-0.044),but there was no statistical difference at 3 months(P = 0.529,0.510),However,the variation of ultrasound of the most serious single target joint in the intermediate-dose prophylaxis group was less than the low-dose prophylaxis group,but there was no significant statistical difference between the two groups after 3 months,6 months,9 months and 12 months(P>0.05).(2)The function of the most serious target joint:follow up 3 months,6 months,9 months and 12 months,the variation of HJHS score of the most serious single target in the three groups were positive,and which of the low and intermediate-dose prophylaxis groups were less than which in the on-demand treatment group,followed up for 6 months,9 months and 12 months.There was a significant statistical difference(P = 0.000-0.030),but only intermediate-dose prophylaxis group was less than which in the on-demand treatment group(P = 0.012)after 3 months of follow-up(P = 0.012),and there was no statistical difference between the low-dose prophylaxis group and the on-demand treatment group(P = 0.189);the variation of HJHS score of the most serious single target joint in the intermediate-dose prophylaxis group were less than low-dose prophylaxis group.There was significant difference after the 12 months of follow-up(P=0.023).There was no significant difference between the two groups after 3 months,6 months and 9 months(P>0.05).5.Quality of life:the CHO-KLAT scores in the three groups were all decreased.The variation of the CHO-KLAT score of the low and interrmediate-dose prophylaxis groups were lower than which of the on-demand treatment group(P=0.000-0.023).The variation of the CHO-KLAT score in the intermediate-dose prophylaxis group was less than which in the low-dose prophylaxis group,and there was a significant difference(P=0.031,0.039).6.The correlation between the clinical hemorrhagic phenotype and the ultrasound and HJHS score of the most severe single target joint ultrasound and the change of the total score of FISH:there was no significant correlation between the annual bleeding rate and the the variation of ultrasonic score of the most serious single target after 12 months in the three groups(P>0.05).There was no significant correlation between the annual bleeding rate and the the variation of HJHS score of the most serious single target after 12 months in the three groups(P>0.05).There was negative correlation between AJBR and the variation of FISH total score after 12 months in the intermediate-dose prophylaxis group(r=-0.539,P=0.014),but there was no significant correlation between AJBR and the variation of FISH total score after 12 months in the on-demand treatment group and the low-dose prophylaxis group(P>0.05).7.The correlation between the variation of HJHS score and the ultrasound and FISH score:There was positive correlation between the variation of ultrasound and HJHS score after 12 months of the most serious single target joint in the low and intermediate-dose prophylaxis groups(r=0.818,P=0.000,r=0.809,P=0.000),but there was no significant correlation in the on-demand treatment group(P=0.878).There was no significant correlation between the the variation of HJHS total score and FISH total score after 12 months in the three groups(P>0.05).8.The correlation between ultrasound and MRI score of the most serious single target joint:in the follow-up of sixth month,there was positive correlation between ultrasound and MRI score in the three groups(r=0.944,0.980,0.953,P=0.000).Chapter two:effected factors of the joint structure and function in children with severe hemophilia A.1.Children of class ?T and class ?T:followed up 12 months.the variation of the ultrasound and HJHS score of the most serious single target joint were positive.The variation of class IT were less than which of class ?T(P=0.000,0.002).2.Children of class ? B and class ?B:followed up 12 months.the variation of the ultrasound and HJHS score of the most serious single target joint were positive.The variation of class ?B were less than which of class ?B(P=0.009,0.007).3.Children of class ?Q and class ?Q:followed up for 12 months.the variation of the ultrasound and HJHS score of the most serious single target joint were positive.The variation of class ?B was less slightly than which of class ? B,but there was no significant difference(P=0.763,0.833).Research main points1.It showed that low and intermediate-dose prophylaxis could not reach the goal without bleeding after 12 months of follow-up,but it could significantly improve the clinical bleeding phenotype,and the number of target joints remained unchanged and few decreased in some children.At the same time,ultrasound score,and HJHS score of the joint and FISH score in the low and intermediate-dose prophylaxis groups were also not reversed,but the damage progress were delayed with the increase of time,and CHO-KLAT score was obviously improved.2.There was no significant correlation between the clinical hemorrhagic phenotype and the variation of ultrasound and HJHS score of the joint and the FISH score,while the ultrasound and MRI score,the HJHS and the ultrasonic score had a good correlation,indicating that the clinical hemorrhagic phenotype was not sufficient to assess the changes of the joint condition.3.The analysis of influence factors suggests that AJBR less than 3 times and perfect joint ultrasound score(joint health status)can more effectively maintain or delay the damage progress of joint structure and function,and the degree of daily life activity does not affect the changes of joint damage. |
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