China ; Hemophilia A ; therapy ; Hemophilia B ; therapy ; Humans ; Quality of Life

Genetic Therapy ; Hemophilia B ; therapy ; Humans

Hemophilia A(HA) is an X-linked recessive bleeding disorder caused by mutations in coagulation factor VIII. Nowadays, exogenous coagulation factor replacement therapy is the main treatment. With the continuous development of gene therapy, new research directions have been provided for the treatment of hemophilia A. CRISPR-Cas9 technology was applied to select suitable target sites, and mediate the targeted knock-in and efficient expression of exogenous B-domain-deleted FⅧ variant gene through corresponding vectors for the treatment of hemophilia A.CRISPR-Cas9 technology is an emerging gene editing tool with great efficiency, safety and effectiveness, and has been widely used in hemophilia gene therapy research. This paper reviews the vector selection, construction of therapeutic genes, gene editing technology and selection of expression target sites for hemophilia A gene therapy at this stage.
Humans ; Hemophilia A/therapy* ; CRISPR-Cas Systems ; Hemophilia B/therapy* ; Gene Editing ; Genetic Therapy ; Genetic Vectors

Anticoagulants ; pharmacokinetics ; Child ; Hemophilia A ; drug therapy ; Hemophilia B ; drug therapy ; Humans ; Precision Medicine

Asian Continental Ancestry Group ; Factor VIII ; Hemophilia A ; therapy ; Hemophilia B ; therapy ; Humans ; Practice Guidelines as Topic

Objective:b> To evaluate the efficacy and safety of a domestic human plasma derived coagulation Factor Ⅸ concentrate (pd-FⅨ) in patients with hemophilia B. Methods:b> The study was a multicenter, open-label and single-arm study. The efficacy of pd-F Ⅸ was evaluated by objective performance criteria. The doses of pd-FⅨ were calculated according to the bleeding symptom and disease severity. The infusion efficiency of pd-FⅨ and improvement of bleeding symptoms were measured at 30 minutes and (24±4) h after the first infusion, respectively. Adverse events were recorded. Viral infection and FⅨ inhibitor were detected 90 d after the first infusion. Results:b> All 36 subjects with hemophilia B were enrolled in the study. The median age of these patients was 31 years old and the median injection doses were 4 (1-17) times. The hemostatic effect of 27/36 (75.00%) and 9/36 (25.00%) acute bleeding events were rated as "excellent" and "better" , respectively. The recovery rate was 111.92% (65.55%-194.28%) at 30 minutes after infusion of FⅨ. There was no adverse event related to FⅨ. No reactivation of HBV, HCV or HIV and FⅨ inhibitor was detected at 90-104 d after the first FⅨ infusion. Conclusion:b> This domestically made human plasma derived FⅨ concentrate is safe and effective in the treatment of acute bleeding in patients with hemophilia B. Clinical trial registration:b> China food and Durg Administration, 2016L08027.
Adult ; China ; Factor IX ; Hemophilia A ; Hemophilia B/therapy* ; Hemorrhage ; Humans ; Plasma

Factor IX/therapeutic use* ; Factor VIII ; Hemophilia A/drug therapy* ; Hemophilia B/drug therapy* ; Humans ; Recombinant Proteins/therapeutic use*

Hemophilia B is an X chromosome linked hereditary hemorrhagic disease, which is caused by the lose function mutation of factor IX (FIX), and significantly affects the patients' lifespan and life quality. The severity of hemophilia B depends on the FIX level in the plasma. By referring to the relevant literatures, we reviewed and summarized hemophilia B replacement therapies. Specifically, we focus on recombinant factor IX products on the market and those in the pipeline, especially on the long-acting factor IX drugs, to provide the basis for researches of new hemophilia B drugs.
Factor IX ; genetics ; therapeutic use ; Hemophilia B ; drug therapy ; Humans ; Mutation ; Recombinant Proteins ; therapeutic use

Adolescent ; Child ; Child, Preschool ; Factor IX ; administration & dosage ; therapeutic use ; Factor VIII ; administration & dosage ; therapeutic use ; Hemophilia A ; drug therapy ; prevention & control ; Hemophilia B ; drug therapy ; prevention & control ; Humans

Hemophilia is the most common coagulation disorder. It has a long history. Hemophilia A is caused by FVIII gene mutation, and hemophilia B by FIX gene mutation. Those genes are located on X chromosome long arm. Bleedings in hemophiliacs predominantly occur in joints and muscles. Because those site are insufficient in tissue factor to induce hemostasis. Among joints knee, ankle and elbow are most frequently affected because their synovial structure is vulnerable to injury compared to other joints. Hemophilia is diagnosed with factor assay. Severe hemophilia is below 1% of FVIII : C, moderate between 1% and 5%, mild over 5%. Carrier detection and prenatal diagnosis have been conducted with RFLP-based linkage analysis and DNA sequencing. Mainstay of treatment is factor replacement therapy so far. Bleedings can be controlled by infusion of factor concentrates. Hemophilc arthropathy and muscle contracture are representative sequelae. Complications of facotor replacement therapy are inhibitor development and infections. Hemophiliacs with inhibitor should be managed with large dose factor concentrate, bypassing agent, ITI and immunosuppression. Ultimately, hemophilia could be cured by gene therapy.
Ankle ; Arm ; Contracture ; Diagnosis ; Elbow ; Genetic Therapy ; Hemophilia A* ; Hemophilia B ; Hemostasis ; Immunosuppression ; Joints ; Knee ; Muscles ; Prenatal Diagnosis ; Sequence Analysis, DNA ; Thromboplastin ; X Chromosome