This year, April 17 marks the 36th World Hemophilia Day, with the theme of "Understanding Bleeding Disorders, Proactive Prevention and Treatment".
Hemophilia is an inherited bleeding disorder caused by the deficiency of coagulation factors, which can be divided into hemophilia A and hemophilia B according to the different types of coagulation factors lacking, which are caused by the deficiency of coagulation factor VIII and factor IX, respectively.
However, there is no clear clinical difference between the two types of hemophilia, both of which manifest as spontaneous bleeding or bleeding that does not stop after minor trauma, and bleeding can occur at any site.
Hemophilia usually develops in childhood. Bleeding in children with severe hemophilia typically manifests as spontaneous muscle and joint hemorrhage, which can be disabling or even fatal if bleeding occurs in the brain, pharynx, or vital areas of the digestive tract.
Long-term and repeated bleeding of joints and muscles can lead to a variety of complications including joint damage, which seriously affects the quality of life of children.
How to prevent bleeding on a daily basis
Children with hemophilia should avoid all kinds of trauma as much as possible in their daily life, and avoid strenuous and especially confrontational sports. If a single joint bleeds repeatedly, the child may wear protective equipment, such as a knee brace for recurrent bleeding from the knee. It should be noted that avoiding various traumatic injuries does not mean that children with hemophilia cannot exercise at all, and daily walking, running, swimming, tai chi and other exercises are allowed. Proper exercise strengthens muscles and better protects joints.
In addition, children should avoid using antiplatelet aggregation or antithrombotic drugs, such as aspirin and clopidogrel. These drugs can worsen bleeding in children with hemophilia. If surgery is necessary, coagulation factors should be transfused to a certain level under the guidance of a hematologist and in accordance with the guidelines, and coagulation factor transfusion should be continued until the wound heals. It is generally believed that for major surgery, children with hemophilia A should be guaranteed to be transfused with 60~80IU/kg (international units/kg body weight) of coagulation factors before surgery, and children with hemophilia B should be guaranteed to be transfused with 50~70IU/kg of coagulation factors.
It is also important for children with hemophilia to be aggressive with regular replacement therapy (prophylaxis). Prophylaxis is to inject a certain dose of coagulation factors at a certain frequency to maintain the activity of coagulation factors at a certain level in the child, thereby reducing the risk of bleeding. Prophylaxis can effectively reduce the occurrence of bleeding and complications in children with hemophilia.
How to effectively stop bleeding after bleeding
The two main types of bleeding in children with hemophilia are joint bleeding and muscle tissue bleeding. The child should be aware of the symptoms of bleeding to avoid further damage caused by delayed detection. Joint bleeding generally has symptoms such as pain, swelling, increased skin temperature, and limited joint movement, and is common in weight-bearing joints such as knees, elbows, and ankles, followed by hips, shoulders, and wrist joints. Muscle tissue hemorrhage often manifests as local muscle pain, swelling, stiffness, bruising of the body surface, increased skin temperature, and corresponding joint mobility disorders.
Once bleeding is detected in a child with hemophilia, the most important thing is to inject clotting factors as soon as possible. Thereafter, care can be carried out according to the RICE method.
"R" (Rest) - rest: the affected side joint rests (> 12~24 hours), and the functional position is immobilized.
"I" (Ice) - ice: 10~15 minutes each time, once every 2 hours.
"C"(Compression)——加压:弹性绑带加压包扎出血关节。
"Elevation" – Elevation: Elevation of the affected limb beyond the heart.
The bleeding site may be accompanied by pain, which is usually significantly relieved with replacement therapy. If the pain is severe, pain medications may be used to relieve symptoms, but drugs that can suppress platelet function, such as aspirin, should be avoided.
How to manage complications related to hemophilia
Recurrent bleeding and coagulation factor transfusions in children with hemophilia can lead to a variety of complications, including hemophilic arthropathy, hemophilic pseudotumors, and factor VIII or IX inhibitor production.
◉ Hemophilic arthropathy refers to impaired joint function or joint deformity due to repeated bleeding from the joint. It is caused by irreversible damage to the articular cartilage due to persistent chronic synovitis and recurrent joint hematomas.
The goal of hemophilic arthropathy treatment is to improve joint function and reduce pain. The decision to proceed with physical therapy or conservative treatment should be based on the child's disease status, symptoms, and treatment conditions. Children with severe joint injuries need to be managed by an orthopedic surgeon.
For adult patients with advanced hemophilic arthropathy, joint replacement can restore joint function and improve quality of life to a certain extent, but orthopedic surgeons need to strictly grasp the indications for surgery.
◉ Hemophilia pseudotumor refers to the repeated intraosseous or subchondral bleeding in children with hemophilia caused by external forces such as impact, which is caused by bone resorption or cystic changes, most commonly in long bones and pelvis. If left unchecked, the pseudotumor may grow in size and erode the tissues adjacent to it. Pseudotumors can form huge masses that compress nerves and blood vessels, causing serious complications such as pathological fractures.
In terms of treatment, for smaller pseudotumors, alternative treatments can be used to observe changes. For larger pseudotumors, they should be removed as soon as possible to avoid continued growth of the pseudotumor and further damage to the surrounding tissues.
◉ After children with hemophilia are transfused with clotting factors, some children may develop autoantibodies against clotting factors, called inhibitors.
Inhibitor production renders conventional coagulation factor transfusions ineffective. The incidence of inhibitors is about 30% in children with severe hemophilia A and about 10% in children with moderate hemophilia B.
After bleeding, high-dose coagulation factor transfusions may be used if the inhibitor titer is ≤5 BU (Bethesda units), and if the inhibitor titer is > 5 BU, a bypass agent such as activated factor VII or prothrombin complex should be used.
Currently, ITI (immune-induced tolerance therapy) is the mainstay of treatment for the removal of hemophilia with inhibitors. ITI refers to the long-term regular treatment of inhibitor-positive children with coagulation factor preparations, so that the coagulation factors can reach peripheral immune tolerance and eliminate inhibitors.
The ITI success rate is approximately 70% in children with hemophilia A inhibitor positive and 30% in children with hemophilia B inhibitor positivity. This method requires long-term, massive infusion of coagulation factors, frequent venipuncture, and is expensive.
As a hereditary disease, children with hemophilia have a lifelong risk of bleeding, so they should fully understand the treatment of bleeding and complications, and treat it in time to avoid irreversible damage. At the same time, the care of children with hemophilia also requires the cooperation of multiple departments and the coordination of relevant departments.
At present, gene therapy, as a treatment that is expected to cure hemophilia, has been marketed abroad, and a number of related clinical trials have been carried out in mainland China, but at present, gene therapy clinical trials are mainly applicable to adult patients, and children should adhere to preventive treatment to maintain healthy bone and joint status, and can receive gene therapy when conditions permit, so as to obtain long-term efficacy or even cure.
Source: Health News WeChat public account
Editor: Guo Lei
Review: Pan Huahong, Yan Yan