1.What is hemophilia? Hemophilia is a group of bleeding disorders caused by hereditary coagulation factor deficiency. Coagulation factors are a group of biologically active proteins in the body that cause blood to clot and have a hemostatic function. There are thirteen major coagulation factors, often expressed in Roman numerals as: I, II ….XIII (i.e. coagulation factors I, II…to XIII). If the blood lacks a certain clotting factor, the blood will not clot easily, thus causing bleeding disorders. 2.What types of hemophilia are there? Hemophilia can be classified according to the type of clotting factor deficiency: (1) Hemophilia A: It is caused by the deficiency of clotting factor VIII (i.e., VIII), also known as hemophilia A. It is the most common type of hemophilia in clinical practice, accounting for about 80%-85% of the number of hemophiliacs, and even higher in some high-incidence areas. (2) Hemophilia B: It is caused by coagulation factor IX (i.e., IX) deficiency, also known as hemophilia B. It is less common than hemophilia A and accounts for about 15% of the hemophilia population. (3) Hemophilia C: lack of coagulation factor XI (i.e., D.D. deficiency, also known as Rosenthal syndrome abroad). D. deficiency is extremely rare in China. (4) Acquired hemophilia (i.e., acquired coagulation factor deficiency): often due to their own factors resulting in decreased levels of certain coagulation factors, or reduced activity, such as acquired coagulation factor VIII (VIII) deficiency, often due to their own production of factor VIII antibodies, resulting in coagulation dysfunction, resulting in acquired hemophilia (hemophilia A). 3. How is hemophilia inherited? Hemophilia A and B are sex-linked recessive disorders, while hemophilia C (hereditary D. deficiency) is an autosomal recessive disorder. In China, hemophilia A is predominant, and the causative gene is located on the X chromosome in women, which means that women carry the gene and cause the next generation of men to develop the disease, while the next generation of women are normal. Therefore, hemophiliacs often have a family history, and the common inheritance pattern is that women get the disease gene from the previous generation (carriers, no disease), and then inherit it to the next generation of men, also known as “intergenerational inheritance”. 4.What are the common symptoms and severity of hemophilia? Typical hemophiliacs often develop coagulation dysfunction since early childhood, spontaneously or after mild trauma, and bleeding cannot be stopped spontaneously; thus, they often bleed more than once during trauma and surgery, and in severe cases, they can also bleed spontaneously after more strenuous activities, especially bleeding joints and muscles, resulting in severe joint swelling and muscle ischemia and necrosis, which can affect the growth and development of bones and joints and lead to joint deformity and muscle Long-term attacks can affect bone and joint growth and development, leading to joint deformities and muscle atrophy, resulting in difficulty in moving the limbs (mainly the lower limbs), and in severe cases, inability to walk. The bleeding characteristics of hemophilia are: (1) bleeding is more frequent: mostly after mild trauma or minor surgery; (2) inherent and lifelong; (3) often manifested as soft tissue or deep intramuscular hematoma; (4) repeated bleeding is prominent in weight-bearing joints such as knee and ankle joints, which may eventually lead to joint deformity, and may be accompanied by osteoporosis, joint ossification and corresponding muscle atrophy (hemophilic joints). (5) The severity of bleeding is related to the type of hematogenesis and the degree of deficiency of related factors. In addition, signs and symptoms of hematoma compression may occur, including: (1) local pain, numbness and muscle atrophy due to hematoma compression of peripheral nerves; (2) symptoms caused by compression of blood vessels and ureters; (3) compression of organs such as the chest and abdominal cavity, affecting the function of internal organs. 5.How to diagnose hemophilia? In addition to the above genetic history and bleeding symptoms, further tests are required: (1) Routine blood tests: normal platelet count, reduced hemoglobin in severe bleeding. (2) Coagulation tests: normal prothrombin (PT) time, prolonged partial thromboplastin time (APTT), significantly prolonged in heavy cases, slightly prolonged in light cases, normal in subclinical cases. (3) Other tests: Clinical confirmation often requires testing of the coagulation activity of VIII. For patients with any degree of hemophilia, complete diagnosis can be further confirmed by genetic testing, such as PCR and gene chip technology, which are commonly used. In addition, other causes of coagulation factor deficiency should also be excluded; for example, bleeding due to coagulation factor deficiency caused by rodenticide poisoning and bleeding caused by anticoagulant drugs such as warfarin. 6.How to treat bleeding in patients with hemophilia? (1) General hemostatic treatment, such as the use of antifibrinolytic drugs and general hemostatic drugs that promote platelet aggregation, etc. For severe bleeding resulting in joint and muscle hematoma, local compression and cold compresses such as bandages or sandbags can be used to stop the bleeding. (2) Coagulation factor replacement therapy: It is the main therapy, i.e. replenishing the missing coagulation factors. The main methods are: ①: fresh frozen plasma (containing all the clotting factors in human blood), ranging from 200-400 ml per day/per time depending on the condition. ②: Plasma cold precipitate (mainly containing VIII and fibrinogen, etc., of which the concentration of VIII is 5-10 times higher than that of plasma), ranging from 10-20 IU (international units) per daily infusion, depending on the condition. ③: Thrombinogen complex (containing X, IX, VII and II), for general replacement therapy. ④: Blood-extracted VIII concentrated preparations, or genetically recombinant activated VIII preparations (different manufacturers, different specifications). The use of coagulation factors: According to the coagulation activity of VIII, it can be based on the following formula: the first input of activated VIII (or IX) dose (IU) = body weight × the level of activity to be increased (%) ÷ 2. The minimum hemostasis requires the level of VIII to reach 20% or more, and for those who have serious bleeding or wish to perform medium-sized surgery or above, the level of activity of VIII or IX should reach 40% or more. ⑤: recombinant human activated factor VII (rFⅦa, activated factor VII): can be used to prevent or treat bleeding in patients with severe hemophilia who are deficient in VIII or IX. The commonly used dose is 90g/kg administered intravenously every 2 to 3 hours until bleeding stops. (3), Drug therapy: less effective than coagulation factor replacement therapy, such as the use of: desmopressin (DDAVP), danazol (danazol) and glucocorticoids to improve vascular permeability, etc. (4), Home treatment: Home treatment for hemophiliacs has been widely used abroad. Hemophiliacs and their families should be educated about the pathology, physiology, diagnosis and treatment of the disease, and home treatment should initially be carried out under the guidance of a medical professional. In addition to teaching injection techniques, it also includes knowledge of hematology, orthopedic surgery, psychiatry, psychology, and prevention of AIDS and viral hepatitis. (5), Surgical treatment: Those with joint bleeding should be treated with alternative treatment along with fixation and physiotherapy. For patients with repeated joint bleeding resulting in joint ankylosis and deformity, arthroplasty or artificial joint replacement can be performed under the premise of replenishing sufficient amount of coagulation factors. (6). Other treatments: such as expression of sufficient amount of clotting factors in patients through different gene therapies, etc. These methods are still in the clinical trial stage and have not been fully used in the clinic. 7. How to prevent bleeding in hemophilia? Prevention of bleeding is more important than substitution therapy, including: (1) strengthening education, avoiding strenuous activities and encouraging appropriate physical activities; (2) avoiding the use of antiplatelet drugs; (3) avoiding intramuscular injections; (4) if surgery is needed, the coagulation factors lacking should be supplemented before surgery; (5) if possible, the corresponding coagulation factors should be supplemented regularly and prophylactically, etc. (6) Hemophilia is a contraindication to many invasive operations, such as tooth extraction, bone penetration, surgery, etc. Avoid blind operations before giving coagulation factor infusion intervention. 8.How can pregnant women with a family history of hemophilia be eugenicized? As the saying goes, prevention is better than cure. Since hemophilia is carried by women leading to the next generation of men, post-pregnancy prenatal diagnosis and eugenics can be carried out. Genetic testing should be done for family members of hemophiliacs, especially for female patients. For women with a family history but no gene carriage, post-pregnancy delivery can safely follow normal procedures. For female carriers, it is best to do gender determination after pregnancy (usually within 12-14 weeks). If the fetus is female, normal full-term delivery can be done according to the heart, while if the fetus is male, DNA extraction such as amniocentesis is needed to detect the severity of hemophilia, or sampling through umbilical cord blood (after about 16-18 weeks of gestation) to determine the degree of clotting factor deficiency, and depending on the actual situation To determine whether to perform a therapeutic abortion procedure, especially in pregnant women with severe fetal clotting factor deficiency, the pregnancy should be terminated as early as possible. In addition, with the current development of the third generation IVF technology, in vitro fertilization can be performed on women who are gene carriers. Through in vitro genetic testing of fertilized eggs, the presence or absence of gene carriers can be determined, so that the healthiest embryos of women without gene carriers can be selected among many embryos and implanted into the mother’s womb to ensure the birth of a healthy baby. Thus, eugenics not only brings post-marital happiness to a family with a family history of hemophilia, but also breeds healthy seeds for the next generation.