Efficacy And Safety Of Recombinant Human Coagulation Factor Ⅷ In The Preventive Treatment Of Severe Hemophilia A In Gansu Province

Objective: To evaluate the efficacy and safety of recombinant human coagulation factor Ⅷ for injection in the prevention and treatment of severe hemophilia A patients in Gansu Province.Methods:1.18 patients with severe hemophilia A in Gansu Province were selected from the First Affiliated Hospital of Lanzhou University.2.Prevention and treatment plan: for non bleeding patients,the initial preventive dose was 25IU/kg,once every other day.In case of bleeding during 24 weeks of prevention and treatment,treatment on demand shall be carried out: required amount(IU)= expected increase value of FⅧ(IU/dL or% normal value)× body weight(kg)× 0.5(IU/kg)/(IU/dL).3.Efficacy indicators:(1)visual evaluation of bleeding prevention and hemostasis:annual bleeding rate(ABR),annual joint bleeding rate(AJBR),annual target joint bleeding rate(ATJBR),hemostasis score after treatment of bleeding events;(2)FⅧactivity level in blood after administration;(3)quality of life evaluation: Hemophilia joint health score(HJHS),European five dimensional health score(EQ-5D).4.Safety index:(1)the occurrence of FⅧ inhibitor;(2)the occurrence of adverse events was evaluated by physical examination,blood routine,urine routine,blood biochemistry,serum virology,electrocardiogram and other laboratory tests.Results:1.General baseline characteristics of case: the median age of 18 patients with severe HA was 23 years(12-47 years),the age of the first hemorrhage was 2.57±3.69 years,the age of the first joint hemorrhage was 5.23±5.78 years,the average age of disease diagnosis was 6.55±7.21 years,the diagnosis delay was 3.98 ± 4.85 years,the age of the first alternative treatment was 7.52±7.68 years,and the age of the first target joint formation was 6.45±6.88 years.5 cases(27.8%)had positive family history.The baseline FⅧ inhibitors were all negative.In the first three months of this study,there were 37 bleeding events,including 35 spontaneous bleeding(95.6%)and2 traumatic bleeding(5.4%);29 joint bleeding(78.4%),2 muscle bleeding(5.4%),1soft tissue bleeding(2.7%)and 5 oral bleeding(13.5%).7 patients(38.9%)had joint deformity,2 of them were involved in one joint,5 of them were involved in two joints.Among the 12 deformities,7(58.3%)were knee joint,3(25.0%)elbow joint,1(8.3%)ankle joint and 1(8.3%)hip joint.The exposure days(EDs)of all patients were more than 150 days.In the past,all patients received FⅧ(plasma derived coagulation factor FⅧ or recombinant coagulation FⅧ)replacement therapy.Two patients used recombinant coagulation factor FⅧ.In this study,18 patients have not received the preventive treatment of the rule of coagulation factor Ⅷ before,and all have received the treatment on demand.Seven patients received surgical treatment,5 cases of joint replacement(1 case of hip replacement,4 cases of knee replacement),2 cases of arthroscopy(1 case of knee arthroscopy,1 case of ankle arthroscopy),1 case of synovectomy,and 3 cases received rehabilitation treatment.2.The FⅧ level in 18 patients after drug infusion was significantly higher than before,and the effective rate was 100%.3.16 of the 18 patients were given preventive treatment for 24 weeks,and the other 2 patients were interrupted at the 4th and 8th week respectively.The patients’ self-control observation showed that the clinical bleeding phenotypes before and after treatment were significantly lower than those after treatment,and there was a significant difference between the two(P<0.01).Before and after treatment,the clinical bleeding phenotype was improved in different age groups,with significant difference(P<0.01).In 12-18 years old group,ABR decreased by 100%,AJBR decreased by 100%,ATJBR decreased by 100%;in 19-65 years old group,ABR decreased by 98.7%,AJBR decreased by 99.1%,ATJBR decreased by 99.3%.4.17 patients(94.4%)achieved zero bleeding,1 patient(5.6%)had two bleeding events.The activity level of FⅧ was 1.1% before the patients were enrolled in thegroup.The two bleeding events were joint hemorrhage after the increase of joint activity,and there was no new site and new joint hemorrhage.After the first occurrence of right shoulder hemorrhage,the dosage of 1500 iu was given under the expected increase value of 50IU/dL of FⅧ,and the joint pain and bleeding symptoms were completely relieved within 4 hours after infusion,and the hemostatic effect score was excellent;the second was the hemorrhage of right elbow and left ankle,and the dosage of 1500 IU under the expected increase value of 50IU/dL of FⅧ was given,and the pain and bleeding were relieved within 8 hours,and the drug was given again24 hours after injection,and immediately The patients’ pain and bleeding were relieved completely and the score of hemostasis effect was good.5.According to the HJHS score before and after treatment,9 patients(50%)had no significant progress in joint disease,9 patients(50%)had aggravation of joint disease,and 1 patient had no improvement in joint disease.After the observation,there was no significant change in the scores and total scores of all aspects of hjhs,and there was no statistical difference before and after treatment(P>0.05),indicating no significant change in joint health.There was no significant difference in the total score of HJHS before and after treatment between the 12-18 years old group and the19-65 years old group(P<0.05).6.The health utility values of 18 patients were obtained by comparing the table of tto utility values in China.Compared with the baseline level of 0.684±0.221 at the time of enrollment,the health utility value of EQ-5D was 0.792±0.133,and the utility value increased(P=0.022<0.05),indicating the improvement of health status.The mean score of EQ-VAS was 68.7±9.8 before prevention and treatment,9 cases(50.0%)with score≥70;14 cases(77.8%)with score≥70 after prevention and treatment,indicating improvement of health.7.There were 1 case,3 cases and 1 case with positive virological HBS Ag,HBS Ab and HCV Ab reports,respectively.The results of virological positive test of the above patients were the results before rhFⅧ treatment,but there was no new relevant virological positive test report in the follow-up after rhFⅧ treatment.There were no significant changes in blood routine,biochemical routine,urine routine and ECG in18 patients after treatment.During the follow-up and after treatment,FⅧ inhibitor was negative.No adverse reactions and adverse events were observed in all patients during the use of recombinant human coagulation factor Ⅷ,which indicated that recombinant human coagulation factor Ⅷ had good safety in the prevention andtreatment of severe HA patients in Gansu Province Complete,no risk of transfusion related virus infection.Conclusion: Using the short-term standard dose of recombinant human coagulation factor Ⅷ in the prevention and treatment of severe hemophilia A patients in Gansu can reduce bleeding,delay joint damage,improve the quality of life,with good effectiveness and safety.