What Is Hemophilia B?

It is characterized by excessive bleeding or spontaneous bleeding after injury to body parts such as weight-bearing joints, soft tissues and mucous membranes. According to the difference of plasma coagulation factor activity and clinical symptoms, patients are divided into three clinical subtypes.

Hemophilia B

Hemophilia B, also known as factor deficiency or plasma thromboplastin deficiency, is a coagulopathy that was first distinguished from hemophilia A by Aggeller in 1952. The ratio of A to B incidence is approximately 5.4: 1. A mutation in the factor VIII encoding gene causes a deficiency in the function of the coagulation factor and causes the disease. It has an X-linked recessive inheritance, and the incidence is about 1/30000 in male live babies.

Clinical manifestations of hemophilia B

Hemophilia B

Plasma coagulation factor activity is less than 1% of normal, and most often manifest as early spontaneous bleeding, repeated spontaneous hematoma, and multiple bleeding in infants and young children. Factor replacement therapy is required to survive for a long time;

Hemophilia moderate

Plasma coagulation factor activity is normal 1 to 5%, mostly manifested as bleeding after surgery or injury;

Hemophilia B

Plasma coagulation factor activity is 5 to 25% normal, clinical manifestations of bleeding after surgery or injury, and spontaneous hematoma are extremely rare.

Hemophilia B diagnosis

Mainly based on family history, clinical manifestations, coagulation tests, and platelet function tests, the diagnosis requires determination of factor activity and genetic diagnosis. The diagnosis of carriers is mainly based on linkage analysis and genetic diagnosis.

Prevention and treatment of hemophilia B

Factor replacement therapy is the fundamental measure for the treatment of this disease. Common substitutes include fresh blood, plasma, and concentrated factor . Preventive replacement therapy for severe patients can prevent spontaneous bleeding and can delay the progression of chronic joint disease. When life-threatening bleeding in important parts of the central nervous system or near the respiratory tract is life-threatening, it is important to quickly administer factor concentrates instead. The application of antifibrinolytic drugs can help prevent bleeding after dental surgery.

Genetic counseling for hemophilia B

Hemophilia B is an X-linked recessive genetic disease that accounts for approximately 10% of hemophilia. Heterozygotes are asymptomatic and are mainly diagnosed by linkage analysis.

Introduction to Hemophilia B Genetics

Hemophilia A and B are recessive on the X chromosome. Women generally do not get sick, but they can carry disease-causing genes. Among the offspring of females carrying normal genes and normal males, men have a 50% chance of developing the disease, and women have a 50% chance of carrying the disease genes. Among the offspring of the affected men and normal women, all men are normal, and all women carry the disease-causing genes. Therefore, these two hemophilia are inherited from generation to generation. Hemophilia C is recessive in autosomal insufficiency.

About 10,000 people will have about one person with hemophilia A, about 35,000 people will have about one person with hemophilia B, and people with type C hemophilia are rare

Hemophilia B treatment and some side effects

Hemophilia B (Hemophilia B) is a coagulopathy caused by a lack of factor IX. Although hemophilia B is a type of hemophilia, the number of people with hemophilia B is much lower than that of patients with hemophilia A, so many doctors don't know What blood products should be used for hemophilia B patients, for example, some doctors will use cryoprecipitate or anti-hemophilia globulin for hemophilia B patients.

Hemophilia B Treatment of Hemophilia B

The treatment of hemophilia is nothing more than blood transfusion, plasma transfusion, and coagulation factors. Where conditions permit, the use of coagulation factors is encouraged. Because the structure of factor IX protein is simpler than that of factor VIII, the repair of gene defects of factor IX is relatively easier than the technology of repair of factor VIII gene defects. The use of gene therapy to treat hemophilia B is also a step ahead, and has entered Clinical trials, but for all patients, the use of various factor IX preparations to control bleeding is still the main method at present. Currently, factor IX products commonly used around the world mainly include thrombin element complexes, pure factor IX extracted from plasma, and pure factor IX synthesized by genetic technology, but currently domestic manufacturers can only produce thrombin element complexes, which contain IX , VII, II and other coagulation factors. Since coagulation factors VII and II are proteins with properties similar to those of factor IX, to obtain pure factor IX, it is necessary to separate again from the thrombin element complex, which requires a more complicated purification process. The introduction of pure factor IX extracted from plasma has appeared on the websites of some manufacturers. It is not too long for domestic patients with hemophilia B to use pure factor IX. After factor IX enters the body, only 50% stays in the blood, and the other 50% goes to other places (it is not entirely clear which organs are currently), so compared with factor VIII, the dosage of factor IX is doubled.

Hemophilia B Thrombin Complex Side Effects-Thrombosis

Many years of clinical application prove that it is safer to input pure factor IX. Just as patients with hemophilia A can self-inject factor VIII, patients with hemophilia B can self-inject pure factor IX, usually without side effects. However, the injection of the thrombin complex may have a serious side effect-thrombosis.

To put it simply, the appearance of blood clots in human blood vessels is thrombosis. Such blood clots may appear in venous blood vessels near the epidermis or in deeper blood vessels in the human body. Deep vascular embolism is a great threat to human life and should be given full attention. Due to the slow flow of blood in the lower limbs of the human body, most deep thrombosis occurs in the legs or buttocks, and thrombosis in the thighs is usually much more severe than thrombosis in the lower legs. If these thrombi fall off from the formation site and move in the blood vessels with blood circulation, they may accumulate in the pulmonary capillaries and form pulmonary embolism, which will be very dangerous and may cause death of the patient.

1) Formation of thrombus

A large amount of thrombin element complex may form vascular embolism, genetic factors, slow blood flow, cancer treatment, varicose veins, prolonged sitting posture during travel, and overweight may all cause vascular embolism.

Although thrombosis is a great threat to hemophilia B patients who use thrombin complexes, under normal circumstances, bleeding is treated at the usual dosage. There are very few cases of thrombin caused by thrombin complexes. Hemophilia patients have been using thrombin complexes for more than 20 years. Most patients have never had a thrombotic reaction, so do not stop using thrombin complexes because of fear of thrombosis. When patients use the complex in large quantities for a short period of time, it may sometimes cause vascular embolism. For example, during surgery, in order to avoid a large amount of bleeding, a compound that is much larger than usual is often used, and the patient will stay in bed for a long period of time after surgery, making blood flow slower, and the possibility of vascular embolism at this time Will increase, and the possibility of embolism is often small when the patient stands up and moves.

2) Symptoms of vascular embolism

Only about 50% of patients with vascular embolism have obvious symptoms. The specific manifestations are significant leg enlargement and leg pain (usually pain in one leg when standing or walking), and there is an enhanced warmth in the swollen leg. Skin redness or color change. In patients with pulmonary embolism caused by vascular embolism, the chest obviously feels pain when breathing deeply and feels shortness of breath.

3) Examination of vascular embolism

Common examination methods are ultrasound and angiography, as well as CT, magnetic resonance imaging and other imaging techniques.

4) Treatment of vascular embolism

When symptoms of vascular embolism occur, you should seek medical treatment as soon as possible. The principle of treatment is to prevent the clot from becoming larger, prevent the clot from falling off and moving to the lungs, and reduce the chance of other embolisms. Anticoagulants are usually used to prevent thrombus enlargement and new thrombosis, such as oral warfarin and injected heparin. These drugs cannot ablate the formed thrombus, but the body itself will gradually dissolve the thrombus. The duration of treatment with these drugs is related to the condition, which may last 3-6 months. During the treatment process, the doctor's advice must be strictly increased or decreased. Because these drugs inhibit the blood coagulation of the human body, incorrect medication may cause serious problems. The bleeding imagination is very dangerous for hemophiliacs. If there are large blood clots that are dangerous to life, thrombolytic agents can be used to dissolve these large blood clots with drugs. Thrombin inhibitors are new drugs that interfere with the coagulation process and can be used in the treatment of some patients. In addition, implanting a filter in the vena cava prevents blood clots from entering the lungs, and using externally pressurized devices to protect the blood vessels in the legs are all methods often used by doctors. It must be noted that during the treatment with drugs such as anticoagulants and thrombolytic agents, the doctor should check the patient's blood coagulation capacity. Overdose of the drug can cause severe bleeding.

Summary of Hemophilia B

Thrombosis may occur when the thrombin element complex is used in large doses in a short period of time. When patients with hemophilia B use the thrombin element complex, the symptoms of thrombosis occur within a few hours or days. Hospital inspection. However, under normal circumstances, hemophilia hemorrhage is treated at the usual dosage, and thromboembolic complexes cause very few cases of thrombosis. The fact that abandoning the thrombin complex to control bleeding is even more dangerous for hemophiliacs.

Scientific research results of hemophilia B

Fudan University and Changhai Hospital jointly tackle gene therapy for hemophilia B

The "Phase I Clinical Study of Hemophilia B Gene Therapy" conducted by the Institute of Genetics of Fudan University and the Department of Hematology of the Changhai Hospital Affiliated to the Second Military Medical University has achieved significant results. After two years of treatment in the world's first two patients with hemophilia B who had undergone gene therapy, the Liu brothers recently came to Changhai Hospital for a physical examination from the North. After a comprehensive inspection by experts such as Professor Meng Peilin, the two brothers were in good health. No side effects or complications related to gene therapy were found. This is by far the only case of hemophilia in the world that has undergone gene therapy, and the results of this research have recently won the second prize for national invention. In the past, hemophilia B could only supplement blood coagulation components through frequent blood transfusions or blood products, but the curative effect was short, the cost was high, and it was threatened by viral infections such as hepatitis caused by blood transfusion. The project "Ethyl Therapy for Hemophilia" funded by the national "863" high-tech development plan uses gene transfer technology to try to fundamentally restore the patient's coagulation function. Scientists and hematologists first culture in vitro fibroblasts taken from patients' skins, at the same time load normal genes that produce clotting factors into vectors, and then transfer the vectors into cultured cells to allow them to multiply. Finally, these cells are embedded in the human body with collagen, which continuously produces coagulation factors and forms normal coagulation functions. According to reports, since 1991, four boys aged 4 to 15 years have been treated with this new technology at Changhai Hospital, and their condition has greatly improved. In two years, the concentration of coagulation factors in the body has doubled. China is the second country in the world to conduct clinical research on gene therapy. How to introduce transgenic cells into patients is one of the key issues in achieving clinical treatment. From the perspective of practicality, convenience and safety, Changhai Hospital pioneered a new method of subcutaneous injection of cell collagen suspension, which is a successful creation. This research has attracted widespread attention from colleagues at home and abroad.