Observation On The Effect Of Individualized Prophylaxis And Treatment In Patients With Severe Hemophilia A Guided By Pharmacokinetics

Objectives The purpose of this study is to determine the pharmacokinetic(PK)parameters of patients with severe hemophilia A,to use PK to guide individualized preventive treatment and to explore its therapeutic effect.Methods Patients with severe hemophilia A who received preventive treatment in the Hemophilia diagnosis and treatment Center of the affiliated Hospital of North China University of Technology from January 2020 to December 2021 were selected.The clinical and follow-up data were analyzed retrospectively.The annual bleeding times(ABR),joint bleeding times(AJBR),annual target bleeding times(ATJBR)and weekly consumption of coagulation factor Ⅷ were recorded.The activity level of plasma coagulation factor Ⅷ was detected 3 hours and 24 hours after infusion of coagulation factor Ⅷ products in all patients.Using the coagulation factor Ⅷ population model analysis software my PKFi T,the PK-related parameters were obtained,including half-life and the time when the weekly coagulation factor Ⅷ activity level was less than 1%.Formulate individualized prevention and treatment plan.Then the patients’ ABR,AJBR,ATJBR and weekly coagulation factor Ⅷ consumption were observed after receiving individualized preventive treatment under PK guidance for 3 months,and the above results were statistically analyzed.Results A total of 18 patients with severe hemophilia A were enrolled,with a median age of 23.5 years(range 18.5～37.5 years).The PK parameters were determined and the treatment regimen was adjusted in all patients,of which the total weekly dose was increased in 13 cases and decreased in 5 cases.The ABR of 18 patients with severe hemophilia A before PK guidance was(39.39±14.77)times per year,and the ABR of individualized preventive treatment after PK guidance was(31.67±11.86)times per year.the difference was statistically significant(P<0.05).The AJBR of preventive treatment before PK guidance was(25.61±8.02)times per year,and the AJBR of individualized preventive treatment after PK guidance was(19.94±8.03)times per year,the difference was statistically significant(P<0.05).and the ATJBR of preventive treatment before PK guidance was(17.61±5.97)times per year,and the ATJBR of individualized preventive treatment after PK guidance was(14.33±5.13)times per year,the difference was statistically significant(P<0.05).The weekly coagulation factor consumption of preventive treatment before PK guidance was 4000(3000～6 000)IU,while that of individualized preventive treatment after PK guidance was 4208(3740～7556)IU.There was no significant difference between the two groups(P>0.05).Conclusions The individualized preventive treatment of patients with severe hemophilia A under the guidance of competition can significantly reduce the number of annual bleeding,annual joint bleeding and annual target joint bleeding,and does not increase the weekly consumption of coagulation factors.Figure4;Table1;Reference 101...