Genetic Detection And Clinical Analysis Of 55 Patients With Hemophilia A In Shandong Province And Effects Of Clinical Trials On Their Quality Of Life

Purpose:1.Analyzing the genetic mutation types of 55 patients with hemophilia A?HA?in Shandong Province to explore the pathogenesis of HA.2.Retrospectively analyzing the clinical characteristics,psychological status and quality of life of 55 HA patients in Shandong Province,and comparing between the mild,moderate and severe group to assess the survival status of HA patients in Shandong Province and analyze related influencing factors to improve Provide assistance for the quality of life of HA patients,and develop the individualized and standardized comprehensive clinical treatment.3.To explore the impact of clinical trials on mental health status and quality of life of HA patients in Shandong Province.Methods:1.LD-PCR?Long-Distance Polymerase Chain Reaction?was used to detect the inversion mutation of intron 22 of coagulation factor ??F??gene in 55 patients with HA in Shandong province,high-throughput sequencing was used to detect the mutation of the 26 exons of F ? gene in the negative-mutation of intron 22,then comparing with the human gene mutation databases.2.Review the case data of 55 HA patients in Shandong Province,using the Chinese version of haemophilia joint health score 2.1?Hemophilia joint health score 2.1,HJHS 2.1?,the hospital anxiety and depression scale HAD),the adult hemophilia patient quality of life assessment questionnaire?Haemo-QoL-A?to evaluate the patient's joint,mental health and quality of life,and analyzing its clinical characteristics.3.Select 55 HA patients enrolled in the clinical trial of drugs in the Department of Hematology of Jinan Central Hospital as the experimental group,and 35 HA patients who were not enrolled in the clinical trial of the drug as the control group.If the patients in the experimental group bleed within the study period,F ? on-demand treatment will be received free of charge,and will be followed up once a month.During the follow-up process,the patient's knowledge of hemophilia was strengthened and updated.At the same time,multi-disciplinary doctors and nurses from the Department of Orthopaedics,Stomatology,Psychology are invited to evaluate the patient's current status.The follow-up lasted a total of 12 months.The patients in the control group still used the individual's previous treatment and received traditional replacement therapy such as plasma and cryoprecipitation infusion,and did not receive follow-up.At the time of enrollment and 12 months after enrollment,the Chinese version of HAD and HaemoQoL-A scales were used to score the psychological status and quality of life of the patients in the experimental group and the control group.Results:1.?20 cases were detected intron 22 inversion,6 cases were.not detected gene mutation,the other 29 cases come from 25 families were totally detected 32?28 kinds?mutation types,3 cases were detected 2 kinds of mutations at the same time.Among them,there were 20 cases?36%?of patients with intron 22 inversion.Among the mutations in the coding region,12 cases?22%?were missense mutations and 7 cases?13%?were nonsense mutations,and there were 6 shear mutations?11%?,4 deletion mutations?7%?,and 3 insertion mutations?5%?.?Among 35 negative-intron 22 inversion cases,all are severe phenotype,6 cases had no gene mutation.Gene mutations of the same family are the same.Compared with NCBI,Pubmed,UCSC,Factor ? Variant Database and so on,9 new mutation types were found.Using SIFT,Polyphen-2 and other biomedical software to evaluate its pathogenic potential,c.2034₂062del,c.6052₆058del,c.6046₆047del were predicted to be pathogenic,c.1009+G>T,c.2997dupA,c.4001delT were predicted to be likely to cause disease,c.1334T>A,c.1493G>A,c.557A>T is uncertain.2.? Of the 55 HA patients,17?30.9%?often live in Jinan,7?12.73%?in Linyi,5?9.09%?in Dezhou,5?9.09%?in Liaocheng,and 4?7.27%?in Binzhou,4 in Heze?7.27%?,3 in Jining?5.45%?,3 in Tai'an?5.45%?,2 in Tengzhou?3.64%?,2 in Yantai?3.64%?,1 in Qingdao,in Rizhao and 1 in Weifang?1.82%?.?14 cases?25.45%?were students,16?29.09%?were employees?11 of which were unstable jobs?,8?14.55%?were farmers,4?7.27%?were freelancers,and 14 cases?25.45%?were unemployed.Of the 43 patients who reached the legal age of marriage?22 years old?in China,30?69.77%?were unmarried,1?2.33%?was divorced,and 12?27.91%?were married?7 of whom had poor marital status?.? 33 cases?60%?were severe patients,22 cases?40%?were moderate,no mild patients.? 26 cases?47.27%?had a clear family history,and the remaining 29 cases?52.73%?had no family history or had unknown family history.10 cases?45.45%?had positive family history in moderate group,and 17 patients?51.52%?had positive family history in the severe.Between the two groups there was no statistically significant difference?P>0.05?.? Between the age of first diagnosis and the age of first bleeding there was statistically significant?P<0.05?.The age of first bleeding,age of first diagnosis,and time of diagnosis delay between moderate and severe group had no statistically significant difference?P>0.05?.?Causes of first bleeding:In moderate group,14 cases?63.64%?were spontaneous bleeding 8 cases?36.36%?were traumatic bleeding.In severe group,27 cases?81.82%?were spontaneous bleeding,6 cases?18.18%?were traumatic bleeding.There was no significant difference in the causes of the first bleeding between the moderate group and the severe group?P>0.05?.First bleeding manifestation:55 patients with HA had the first episode of bleeding in the following order:joint bleeding?60%?,skin and mucous membrane bleeding?30.9%?,gum bleeding?3.6%?,and muscle,visceral,and intracranial bleeding were the least,each accounting for 1.8%.There was no significant difference in the first episode of bleeding between the medium and heavy group patients?P>0.05?.First degree of bleeding:8 cases?36.36%?had mild bleeding,13 cases?59.09%?had moderate bleeding,and 1 case?4.55%?had severe bleeding.In severe cases,cases?33.33%?had mild bleeding,21 cases?63.64%?had moderate bleeding,and 1 case?3.03%?had severe bleeding.There was no significant difference in the degree of bleeding between medium and severe patients?P>0.05?.?The average joint score of the moderate group was 23.68 points,and the average joint joint score of the severe group was 23.33 points.Between the two groups there was no statistically significant difference in HJHS2.1 scores?P>0.05?.?Of 55 patients with HA,13?23.64%?were treated only for severe bleeding,42?76.36%?were treated on demand,and there were no patients with preventive treatment.3 patients had a history of surgery,of which 2 patients underwent knees replacement and 1 patient underwent knee synovectomy.39 cases?70.91%?were treated with cryoprecipitate,plasma or whole blood.? Among 55 patients with HA,the average score of the A scale of the moderate group was 8.86 points,the average score of the A scale of the severe group was 9.61 points;the score of the D scale of the moderate group was 8.96 points and the score of the D scale of the severe group was 9.64 points.Between the,two groups there was no statistically significant difference in the scores of A scale and D scale?P>0.05?.?The average score of the moderate was 95.64 points,and the average score in the severe was 101.30 points.Between the two groups there was no significant difference in Haemo-QoL-A scores?P>0.05?.3.12 patients in the experimental group were lost to follow-up,and 3 patients in the control group were lost to follow-up.The lost patients were not included in the statistical scope.There was no statistically significant difference between the experimental group and the control group in terms of age composition ratio and proportion of moderte and severe types?P>0.05?.There was no significant difference in the first score comparison between the HAD and Haemo-QoL-A Chinese version scales of the two groups of patients?P>0.05?;the last score of each scale in the experimental group was compared with the first score respectively,and the difference was statistically significant?P<0.05?,the last score of each scale of the control group was compared with the first score respectively,and the difference was not statistically signi ficant?P>0.05?.Conclusion:1.? In this study,intron 22 inversion detection and all-exon high-throughput sequencing were performed on the F ? gene of 55 patients in Shandong Province,and it was confirmed that intron 22 inversion usually leads to a severe phenotype and the missense mutation is the most common types of mutations in coding region mutations.?C.2034₂062del,c.6052₆058del,c.6046₆047del,c.1009+1G>T,c.2997dupA,c.4001delT,c.1334T>A,c.1493G>A,c.557A>T,etc.were first discovered.These new mutation types enriched the human F ? gene mutation database and provided a basis for carriers and prenatal diagnosis in the same family.2.?The rate of patient visit depends on the distance and convenience of the visit.Patients generally have delayed diagnosis.There is no difference in the diagnosis of patients between the moderate and severe.?The first bleeding in patients with HA is mostly spontaneous,followed by traumatic;the first bleeding is most common in joint bleeding;whether there is a clear family history has nothing to do with the clinical phenotype;There is no difference in the cause,performance,degree of first bleeding,joint condition and risk of complications between the moderate and severe.?HA patients have not reached the goal of comprehensive treatment such as preventive treatment and rehabilitation.?Marriage and employment of HA patients are not optimistic,anxiety and depression generally exist,and the quality of life is still in the low or middle levels.There is no difference in psychological status and quality of life between the moderate and severe.3.Clinical trials can effectively improve patients' psychological health condition and quality of life.Participating in drug clinical trials can enable patients to receive timely and adequate on-demand treatment.Free trial of blood clotting factor also relieves patients' financial pressure to some extent.At the same time,participating in drug clinical trials involves multidisciplinary experts,regularly follow-up patients,to ensure the implementation of comprehens-ve care,and can timely adjust the treatment plan according to the dynamic changes of the patient's condition.The above guarantees the improvement of patients' psychological status and quality of life in clinical trials of drugs.