Objective:To evaluate the long-term efficacy and safety of recombinant coagulation factor Ⅷ (Octocog alfa) in Chinese patients with hemophilia A (HA) enrolled in the International Antihemophilic Factor Hemophilia A Outcome Database (AHEAD) study (NCT02078427) .Methods:Enrollment of Chinese patients in the AHEAD study was completed by January 2021, and data were collected up to July 15, 2022. This study primarily assessed patients in terms of the Gilbert score, global gait score within the Hemophilia Joint Health Score (HJHS), annualized bleeding rate (ABR), annualized joint bleeding rate, and adverse events.Results:A total of 168 male patients were included in this study, of which 113 received prophylactic treatment and 53 received on-demand treatment. The average age of the patients was 21.4±13.37 years. Compared with baseline, the global gait score within HJHS significantly decreased during the 1-year follow-up in patients with moderately severe HA in the prophylactic treatment group ( P=0.01) and on-demand treatment group ( P=0.008). The mean reduction in Gilbert score was greater in the prophylactic treatment group than in the on-demand treatment group (28.6% vs 8.2%). The average ABR decreased significantly during the 1-year follow-up (3.70 vs 7.78, P=0.01) in the prophylactic treatment group, particularly in patients with severe HA (2.14 vs 8.98, P=0.006) and pediatric patients (2.1 vs 4.73, P=0.03). The ABR score also decreased significantly in the moderate-dose prophylactic treatment group ( P=0.015). During the 1-year follow-up, 25 patients (14.9%) reported 39 adverse events, with only one patient developing treatment-related F Ⅷ inhibitor. Conclusion:Joint mobility improved in patients receiving either prophylactic or on-demand Octocog alfa. Bleeding episodes significantly reduced in patients receiving prophylactic treatment, particularly in pediatric patients and those with severe HA.

Central venous access device-related thrombosis (CRT) refers to the obstructive or non-obstructive clots formed around the central venous access device (CVAD).It may lead to risks such as loss of vascular access, pulmonary embolism, post-thrombotic syndrome.Due to the heterogeneity of underlying diseases and the specific characteristics of CVAD placement in children, there is insufficient evidence for the diagnosis and treatment of CRT in children.This article reviews the diagnosis, treatment and prevention of CRT in children to provide reference for clinical management.

Central venous access device-related thrombosis (CRT) refers to the obstructive or non-obstructive clots formed around the central venous access device (CVAD).It may lead to risks such as loss of vascular access, pulmonary embolism, post-thrombotic syndrome.Due to the heterogeneity of underlying diseases and the specific characteristics of CVAD placement in children, there is insufficient evidence for the diagnosis and treatment of CRT in children.This article reviews the diagnosis, treatment and prevention of CRT in children to provide reference for clinical management.

Objective:To evaluate the long-term efficacy and safety of recombinant coagulation factor Ⅷ (Octocog alfa) in Chinese patients with hemophilia A (HA) enrolled in the International Antihemophilic Factor Hemophilia A Outcome Database (AHEAD) study (NCT02078427) .Methods:Enrollment of Chinese patients in the AHEAD study was completed by January 2021, and data were collected up to July 15, 2022. This study primarily assessed patients in terms of the Gilbert score, global gait score within the Hemophilia Joint Health Score (HJHS), annualized bleeding rate (ABR), annualized joint bleeding rate, and adverse events.Results:A total of 168 male patients were included in this study, of which 113 received prophylactic treatment and 53 received on-demand treatment. The average age of the patients was 21.4±13.37 years. Compared with baseline, the global gait score within HJHS significantly decreased during the 1-year follow-up in patients with moderately severe HA in the prophylactic treatment group ( P=0.01) and on-demand treatment group ( P=0.008). The mean reduction in Gilbert score was greater in the prophylactic treatment group than in the on-demand treatment group (28.6% vs 8.2%). The average ABR decreased significantly during the 1-year follow-up (3.70 vs 7.78, P=0.01) in the prophylactic treatment group, particularly in patients with severe HA (2.14 vs 8.98, P=0.006) and pediatric patients (2.1 vs 4.73, P=0.03). The ABR score also decreased significantly in the moderate-dose prophylactic treatment group ( P=0.015). During the 1-year follow-up, 25 patients (14.9%) reported 39 adverse events, with only one patient developing treatment-related F Ⅷ inhibitor. Conclusion:Joint mobility improved in patients receiving either prophylactic or on-demand Octocog alfa. Bleeding episodes significantly reduced in patients receiving prophylactic treatment, particularly in pediatric patients and those with severe HA.

Objective:To analyze the clinical characteristics of eosinophilic lung diseases(ELD) in children to enhance pediatricians′ understanding of ELD.Methods:In this retrospective cross-sectional study, a total of 149 children with ELD were recruited from Beijing Children′s Hospital, Capital Medical University between April 1, 2007 and March 31, 2022.Chi-square test, Fisher′s exact test, Mann-Whitney U test and Kruskal-Wallis test were used to analyze data and conclude clinical characteristics.Spearman correlation was used to analyze the correlation between eosinophils in peripheral blood and bronchoalveolar lavage fluid.Chi-square test and Kappa consistency test were used to compare the differences and consistency in diagnostic results between bronchoalveolar lavage fluid or lung biopsy and eosinophil elevation with chest imaging abnormalities. Results:(1)The isolated lung involvement was mostly caused by allergic bronchopulmonary aspergillosis(9 patients), and other system involvement by idiopathic hypereosinophilic syndrome(89 patients).(2)The main respiratory manifestations included coughing(90 cases, 60.4%) and expectoration(41 cases, 27.5%), while 23.5%(35 cases) of patients had no respiratory symptoms; 50.3% had digestive system involvement, and 40.9% had skin involvement.These were the two most commonly affected organs.(3)Spearman correlation was performed between eosinophils in peripheral blood and bronchoalveolar lavage fluid( r=0.3, P<0.05).Chi-square test was performed to compare ELD diagnosed by bronchoalveolar lavage fluid or lung biopsy with peripheral blood eosinophilia accompanied by abnormal chest imaging( P<0.05).Kappa consistency test(Kappa<0.2) showed poor consistency between the two diagnostic methods. Conclusions:ELD are present in children, and multiple etiologies may be pathogenic.Among children with ELD, the isolated lung involvement is mainly caused by allergic bronchopulmonary aspergillosis.The digestive system and skin are the most commonly affected organs, except for lungs.The correlation between eosinophil levels in peripheral blood and bronchoalveolar lavage fluid is poor.

Objective To investigate the status quo of family treatment needs of hemophilia in children,and analyze its influencing factors.Methods The convenience sampling method was adopted.The parents of children patients with hemophilia registered on the xueyou website(web.bjxueyou.cn)from June to July 2023 were selected as the research subjects.The survey was conducted in the form of electronic questionnaires pushed by mobile phone text messages.The family treatment needs for hemophilia in children and the influen-cing factors were analyzed.Results A total of 430 parents of children with hemophilia filled in the question-naire,and 409 valid questionnaires were collected,with an effective recovery rate of 95.12％.In the family treatment needs,there were 389 cases(95.11％)of first aid management need of the children patients with hemophilia,386 cases(94.38％)of pain management need,383 cases(93.64％)of bleeding health education need,382 cases(93.40％)of blood vessel protection need,380 cases(92.91％)disease and treatment related records need,375 cases(91.69％)of psychological care need,369 cases(90.22％)of family treatment basic knowledge need,362 cases(88.51％)of self-injection related operations need and 360 cases(88.02％)of daily life guidance need.The multivariate logistic regression analysis results showed that family monthly income 10 000-＜15 000 Yuan(OR=4.297),family monthly income ≥15 000 Yuan and degree in disease severity(OR=3.609)were the positive stimulative factors of family treatment need in children patients with hemo-philia(P＜0.05),the parental cultural degree being undergraduate or above(OR=0.186)and drug adminis-tration tool being PICC or transfusion harbor(OR=0.113)were the negative interventional factors of family treatment need in children patients with hemophilia(P＜0.05).Conclusion The family treatment need in the children patients with hemophilia is high,and it is needed to conduct the orientation health education according to the family characteristics of different children patients in order to increase the family treatment level.

Beijing Children's Hospital affiliated to the Capital Medical University set up a three-tiered system for hemophilia and explore solutions for local and remote referral modes.Through the establishment of electronic database,improving drug management,assisting medical insurance reimbursement and other auxiliary measures,it smooths the two-way referral path of children with hemophilia.It can rationally allocate medical resources,promote the development of local professional medical ability,make rational use of rare disease drugs,improve the efficiency of medical insurance funds,strengthen the service capability of children with rare diseases through the joint reform of three medical systems,and ensure the treatment of difficult and severe child patients,improve the accessibility of high-quality diagnosis and treatment,effectively reduce the financial burden of patients.

Hereditary thrombocytopenia(HT)is a hemorrhagic disease characterized by thrombocytopenia caused by genetic variation.HT can be manifested as simple thrombocytopenia or combined syndrome, and its clinical manifestations are complex.It often occurs in children.The unique clinical characteristics of HT are platelet dysfunction, unstable course of the disease and susceptibility to other diseases.Due to different pathogenic genes, the treatment and prognosis of HT are diverse.The evaluation of hemorrhage in the clinical management of HT children is very important.In addition, platelet transfusion, thrombopoietin receptor agonists, hematopoietic stem cell transplantation and gene therapy also supply new ideas for HT treatment.This review summarized the current research progress on HT, in order to help clinicians comprehensively identify HT and take active and effective treatment programs.

Objective:To analyze the clinical manifestations, genetic variations, diagnosis and treatment of children with inherited thrombophilia(IT).Methods:Retrospective study.Children with IT treated in Department of Respiratory Diseases 1 of Beijing Children′s Hospital, Capital Medical University from October 2016 to August 2021 were included in the study and followed up.Results:A total of 5 children met the inclusion criteria, with 3 boys and 2 girls; the age of diagnosis ranged from 7 years to 13 years and 6 months.There were 2 cases of protein C deficiency, 1 case of congenital protein S deficiency, 1 case of activated protein C resistance and 1 case of congenital afibrinogenemia.All 5 cases had pulmonary embolism, 2 cases had deep venous thrombosis of lower limbs, and 1 case had cardiac thrombosis and arterial embolism.The level of protein C was significantly decreased in 1 case, and the level of protein S in 1 case was significantly decreased in the laboratory test of thrombophilia; 2 cases were positive for antiphospholipid antibodies in the acute phase, but negative after 3-6 months of re-examination.Genetic analysis showed 2 cases of PROC gene mutation, 1 case of PROSI gene mutation, 1 case of F5 gene mutation, and 1 case of FGA gene mutation.All children were treated with anticoagulation drugs for long-term, including 4 patients with Warfarin and 1 patient with Rivaroxaban.The follow-up time ranged from 3 months to 5 years.During the follow-up, 1 patient experienced thrombosis recurrence due to infection incentives 1 month after discontinuing anticoagulant drugs on his own. Conclusions:The clinical manifestations of children with IT are the same as those of adults, mainly including venous thromboembolism(VTE); there are limitations in laboratory detection of thrombophilia, and gene analysis is of great significance.Children diagnosed with IT need long-term anticoagulant therapy to reduce the recurrence of VTE.

Being a hereditary bleeding disorder, hemophilia is characterized by spontaneous bleeding, especially joint bleeding. The treatment outcome is a comprehensive evaluation system of the following three aspects: bleeding, musculoskeletal structure (imaging), and function-activity participation. Multidisciplinary testing and corresponding scales are needed in the assessment. Among them, the quality of life assessment of hemophilia patients is particularly important, through general questionnaires and hemophilia-specific questionnaires. Canadian hemophilia outcomes-Kids' life assessment tool(CHO-KLAT), a special quality of life assessment tool for children with hemophilia, is the most widely used. This paper briefly describes the development and application of comprehensive evaluation system of the children with the disease.