On World Hemophilia Day, caring for "glass people" starts with understanding hemophilia

In order to commemorate the contribution of Mr. Frank Schnabel, the founder of the World Federation of Hemophilia, to hemophilia patients and to alert the public to the correct understanding of hemophilia, April 17th of each year has been designated as World Hemophilia Day since 1989. However, many people feel unfamiliar when they hear about hemophilia and do not know much about it.

Hemophilia is a rare disease. A small wound can cause bleeding that won’t stop, and replacing a tooth can be fatal... Even a slight injury can cause great harm to the body of a hemophiliac, so hemophiliacs are also called "glass people." If not treated in time, they may become disabled or even lose their lives.

Today is World Hemophilia Day. We have specially invited Mr. Wang Wensheng, chief physician of the Department of Hematology at Peking University, to answer questions for us so that we can learn more about hemophilia and care for the "glass people" around us.

1. The situation of hemophilia is very serious

At present, there is no systematic epidemiological study on hemophilia in China. According to relevant literature reports: the prevalence of hemophilia in the United States, the United Kingdom, Switzerland, France, Finland and Japan is 10/100,000, 6.9/100,000, 6.6/100,000, 6.3/100,000, 5.0/100,000 and 2.3-2.6/100,000 respectively. According to literature screening and information extraction, the prevalence of hemophilia in mainland China is about 2.7/100,000. However, the current registration rate of hemophilia in my country is still at a low level.

In addition, it should be noted that the current prevalence and number of patients are only based on relevant literature and information extraction, and lack actual investigation and research support. The prevalence and number of patients with hemophilia may be higher than the existing data.

Affected by various factors, most hemophilia patients in China do not receive timely, comprehensive and systematic diagnosis and treatment, or there are problems such as misdiagnosis, resulting in a joint deformity rate of up to 70% in hemophilia patients over 30 years old.

2. What is hemophilia?

Hemophilia is a group of inherited bleeding disorders caused by gene mutations, resulting in a lack of coagulation factors, which leads to abnormal coagulation function. Generally, 70% of patients have a family history. Clinically, hemophilia is divided into hemophilia A (deficiency of coagulation factor VIII) and hemophilia B (deficiency of coagulation factor IX). Among them, hemophilia A is more common, about 7 times that of hemophilia B.

Hemophilia is characterized by prolonged clotting time and a tendency to bleed. Even minor trauma can lead to more severe bleeding, and severe patients may experience spontaneous bleeding in the absence of trauma.

3. Hemophilia is hereditary

Hemophilia is an X-linked recessive genetic disease.

Hemophilia A and hemophilia B are inherited in the same way, both are X-linked recessive inheritance, occurring in males and passed on by females. The inheritance results can be as follows:

Genetic result 1: The boys born to a male hemophiliac and a normal female are normal, but the girls are all transmitters, that is, they carry the hemophilia gene.

Genetic result 2: Female transmitter and normal male: The boy born from the two may be a hemophiliac or a normal one; however, the girl born has a 50% chance of being a transmitter and a 50% chance of being a normal one.

Genetic result 3: For a male hemophiliac and a female transmitter, the probability of a boy born to the disease is about 50%, that is, about half of the boys born are normal; among the girls born, they may be hemophiliacs or transmitters, that is, no girls are normal.

Genetic result 4: Both the man and the woman are hemophiliacs, and all their children will be hemophiliacs.

4. What causes hemophilia?

Under normal circumstances, capillaries contract after bleeding to slow down bleeding. At the same time, platelets form hemostatic plugs to fill the damaged capillaries. Then, multiple coagulation factors in the plasma work together to form a firm fibrin block on the basis of preventing thrombosis, achieving the effect of hemostasis.

Coagulation factors include coagulation factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX, X and XI. Any reduction in the content or function of any coagulation factor will weaken the coagulation function and prolong the bleeding time. Congenital defects of coagulation factors VIII and IX are hemophilia.

In addition to genetic factors, gene mutation is also a major factor leading to the onset of hemophilia.

Beware of acquired hemophilia

Classic hemophilia is a hereditary deficiency of FVIII and FIX, while acquired hemophilia is a bleeding disease caused by the production of specific antibodies against the patient's own coagulation factors in patients with normal coagulation function, resulting in reduced coagulation factor activity in plasma.

Acquired hemophilia is a relatively rare autoimmune bleeding disease. It is estimated that its annual incidence is about 1.5/1 million, and it tends to rise with age. Relevant data show that there are two peaks in the age of onset of acquired hemophilia, namely the first peak of 20-40 years old, which is mainly seen in women of childbearing age, and its onset is related to pregnancy, perinatal period and autoimmune diseases. About 85% of patients develop the disease at the age of 65 or above, forming another peak of onset, which is more common in men than in women, and is mainly related to lymphatic system diseases and tumor diseases.

5. What are the clinical manifestations of hemophilia?

Abnormal bleeding that occurs repeatedly from early childhood is the typical clinical manifestation of hemophilia. The clinical manifestations of hemophilia A and hemophilia B are basically similar and difficult to distinguish.

1. Bleeding

Children with hemophilia usually have their first bleeding at the age of 1-2 years old. The main symptoms are skin bruises on the buttocks and knees after they start sitting and crawling, and joint swelling after they start standing and walking. Hemophilia often causes spontaneous bleeding. Bleeding after minor trauma or surgery is also common. For example, children with hemophilia bleed more and longer than normal children when their skin is scratched or their teeth are replaced. With age, this spontaneous bleeding will become more and more frequent, and the number of bleeding sites will increase.

Joint bleeding

Joint bleeding accounts for 70%-80% of all bleeding in hemophilia patients. It is the most common and characteristic bleeding manifestation in hemophilia patients. It is worth noting that joint bleeding is the main cause of disability in hemophilia patients.

According to authoritative statistics, the joints most commonly affected by joint bleeding in hemophilia patients are: knee joints, ankle joints, elbow joints, hip joints, shoulder joints and wrist joints. The joints where bones meet are wrapped by synovial membranes, which contain many capillaries. When a joint is damaged, the capillaries in the synovial membrane will rupture and bleed, and blood will enter the joint cavity, causing redness, swelling and pain in the joint. The pain is obvious when walking, and most patients will have difficulty walking.

Due to repeated bleeding in the joints, the blood in the joint cavity will stimulate the synovium and cause synovitis. The thickened synovium due to inflammation will aggravate the bleeding due to squeezing and tearing during activities, thus forming a vicious cycle and developing into chronic synovitis, causing patients to experience persistent joint swelling and movement disorders. In addition, repeated bleeding in the joints will also cause irreversible damage to the articular cartilage and bones, leading to hemophilic arthropathy. Patients will experience joint movement disorders, persistent pain, and even joint deformities.

Muscle bleeding

Muscle bleeding is mainly seen in the thigh muscles, calf muscles, biceps, forearm muscles and gluteal muscles. It can be spontaneous bleeding or occur after injury, such as after a blow, sudden stretch, sprain or intramuscular injection.

Muscle bleeding caused by hemophilia does not affect a single muscle, but usually a group of muscles. When muscle bleeding occurs, patients feel muscle stiffness, pain, swelling, increased skin temperature, and the pain worsens when moving or touching.

The swelling caused by muscle bleeding can also compress the nerves in the corresponding parts, blocking blood flow and reducing oxygen supply, causing tingling, numbness or pins and needles in the affected parts. If not treated in time, it can cause permanent nerve damage, muscle necrosis and even deformity.

If the muscle bleeding site is close to the skin, the skin will turn purple within 1-2 days of bleeding. Repeated bleeding will cause scar tissue hyperplasia in the muscles, accompanied by muscle weakness. Some patients will develop pseudotumors due to repeated muscle scar hyperplasia.

Since muscle bleeding is often accompanied by muscle weakness, the patient's activities will be reduced accordingly, causing muscle atrophy, which further aggravates muscle weakness to a certain extent. Muscle atrophy and muscle weakness make the muscles lose their protective effect on the joints, indirectly causing or aggravating joint bleeding.

It can be seen from this that if muscle bleeding is not treated promptly and effectively, it will cause permanent damage to the muscles, nerves and joints, eventually leading to joint deformities, affecting sitting, standing and walking postures, and affecting the patient's normal life.

Bleeding in the head or central nervous system

Bleeding in the head or central nervous system is a more serious type of bleeding and is the main cause of death in hemophiliacs, especially children.

After bleeding in the head or central nervous system, the patient will experience symptoms such as headache, nausea, vomiting, drowsiness, and impaired consciousness. When hemophiliacs experience the above symptoms, especially after head trauma, and the symptoms are very obvious or progressively worsen, they must be treated promptly.

Bleeding in the throat and neck is also a major cause of death in hemophiliacs. Because the hematoma formed after bleeding in the throat and neck will compress the esophagus and trachea, causing difficulty in swallowing or breathing, timely treatment measures must be taken at this time.

In addition, gastrointestinal bleeding and urinary tract bleeding are also common bleeding symptoms in hemophilia patients. Patients will experience symptoms such as vomiting blood, melena, gross hematuria, and some patients will even experience anemia.

2. Compression symptoms and complications of surrounding tissues caused by bleeding

Peripheral nerve involvement: The incidence rate is 5%-15%. Patients feel numbness and pain, accompanied by varying degrees of muscle atrophy.

Upper airway obstruction: Severe bleeding in the mouth, throat or neck can form hematomas and compress surrounding tissues. In severe cases, it may even cause suffocation and endanger the patient's life.

Compression of surrounding blood vessels: When blood vessels are compressed, the blood and oxygen transport to tissues is blocked, which can lead to tissue necrosis.

3. Clinical manifestations of acquired hemophilia

The most common clinical manifestation is that patients with no history of bleeding disorders have spontaneous or severe diffuse bleeding after minor injuries. Bleeding in patients with acquired hemophilia is generally in multiple sites, such as muscle bleeding, gastrointestinal bleeding, cerebral hemorrhage, and oropharyngeal bleeding, with spontaneous subcutaneous hematoma and extensive skin ecchymosis being the most common.

Acquired hemophilia causes severe bleeding, and joint bleeding is relatively rare. Fatal bleeding is the main clinical manifestation of acquired hemophilia. However, according to patient data from the European Acquired Hemophilia Registry, about 7% of patients did not have bleeding in any part of the body when they registered, but only discovered it during blood tests.

6. If a child is prone to repeated bleeding since childhood, does it mean hemophilia?

If a child is prone to bleeding since childhood, it does not necessarily mean that hemophilia. Diseases that cause children to bleed repeatedly mainly include thrombocytopenia, vascular hemophilia, hereditary coagulation factor deficiency, and vitamin K-dependent factor deficiency. Among them, thrombocytopenia is the most common bleeding disease. Therefore, if a child is prone to repeated bleeding, it cannot be directly judged that the child has hemophilia. Instead, a hematologist needs to make a comprehensive diagnosis based on the child's symptoms, test results, family genetic history, and even genetic testing to determine it.

However, if a boy has recurrent bleeding, especially if there is a male relative on his mother's side of the family with a bleeding tendency since childhood, he may have hemophilia and should be taken to a professional medical institution for diagnosis.

7. How to deal with hemophilia?

1. Treatment of bleeding

General hemostatic treatment

For example, antifibrinolytic drugs and general drugs that promote platelet aggregation can be used to stop bleeding. If the joint and muscle hematoma is caused by severe bleeding, cold compress, bandage pressure dressing or local compression hemostasis can be used to stop bleeding.

Coagulation factor replacement therapy

Coagulation factor replacement therapy is the main method for treating hemophilia bleeding. For bleeding in any part of the body, coagulation factor replacement therapy should be given as soon as possible. The earlier the infusion, the better the hemostatic effect, and it can also effectively prevent a series of harms to joints and muscles caused by bleeding.

As the number of bleeding episodes increases, many hemophiliacs can feel the presence of joint bleeding through tingling in the joints, increased skin temperature, etc. before the obvious symptoms of hemarthrosis appear. This is also the best time to infuse coagulation factors, and a small amount of coagulation factors can have a good hemostatic effect.

Currently, coagulation factor replacement therapy is still the main method for treating hemophilia, but there are risks such as viral infection, induction of inhibitors, and phlebitis caused by repeated intravenous injections. The emergence of new coagulation factors and new drugs such as bispecific antibodies can effectively reduce the above risks to a certain extent.

2. Family therapy

Hemophilia is a group of genetic diseases, so hemophilia patients and their families must receive education on disease-related knowledge. Family treatment is the transfusion of coagulation factors by family members after bleeding occurs, as well as the completion of hemophilia care and rehabilitation at home. If conditions permit, hemophilia patients can receive family treatment. Correct family treatment can allow children to obtain coagulation factors immediately and receive timely treatment. However, family treatment can only be implemented after the family members have been fully educated and trained, and it must be performed under the guidance of professional physicians.

3. Surgical treatment

(On March 20, 2015, Tianjin First Central Hospital completed the first knee replacement surgery for a hemophilia patient in Tianjin.)

If hemophilia patients suffer from joint ankylosis and deformity due to repeated joint bleeding, arthroplasty or artificial joint replacement can be performed on the premise of supplementing sufficient coagulation factors. Surgical treatment can effectively relieve the patient's joint pain symptoms, correct joint deformity, and effectively improve the patient's quality of life.

4. Rest, ice, immobilization, compression or elevation of the affected limb

When treating hemophilia patients, in addition to coagulation factor replacement therapy, appropriate treatment methods such as rest, ice compress, immobilization, compression or elevation of the affected limb should be adopted during the acute phase of joint and muscle bleeding.

rest

If the bleeding site is in the leg, the patient should avoid walking independently and should use crutches or a wheelchair. If the bleeding site is in the arm, a sling can be used to support the arm. Although rest is important for bleeding patients, it should be noted that rest is only needed when the limb is bleeding. The limb that is not bleeding should continue to be used to avoid muscle atrophy or joint dysfunction.

Ice

Hemophilia patients should not apply heat when bleeding, as heat will aggravate bleeding. Instead, ice should be applied. Ice can promote vasoconstriction and slow blood flow. At the same time, ice can also help relieve pain and muscle spasms. The ice method must be correct. It is best to wrap an ice bag with a towel and apply it once every 4-6 hours for 15-20 minutes. The ice time should not be too long to avoid frostbite.

oppression

When hemophiliacs experience joint pain and swelling, they can use elastic stockings or elastic bandages appropriately. This helps to relieve pain and swelling in joints and muscles, and provides a certain support to the injured area, which helps to reduce the patient's discomfort.

Elevate the affected limb

Elevating the affected limb so that the bleeding site is above the heart can help reduce the amount of bleeding and relieve swelling.

5. Rehabilitation

After the limb bleeding stops, appropriate physical and rehabilitation therapy can be performed to help restore joint and muscle function. Rehabilitation therapy should start with light exercise, with the main goal of restoring the extension and contraction function of joints and muscles.

(A patient with sequelae of cerebral thrombosis performs lower limb rehabilitation training on a treadmill.)

Then, according to the patient's specific situation, choose different exercise methods to exercise and strengthen muscle strength. During rehabilitation treatment, it should be completed under the guidance and supervision of a physical therapist. If the patient's condition requires, prophylactic infusion of coagulation factors can also be performed before rehabilitation training.

Many people believe that exercise will aggravate bleeding in hemophilia patients, but this view is wrong. In fact, proper exercise can help hemophilia patients prevent bleeding and joint injuries. Moderate exercise can also help reduce patients' tension, anxiety and depression. Hemophilia patients can participate in sports such as swimming, table tennis, walking, fishing, dancing, billiards and cycling. Strenuous exercise is not recommended for patients with severe hemophilia. It is best to listen to the advice of professional doctors on what type of exercise can be performed.

In addition, it is worth mentioning that preventive treatment of hemophilia is the first choice for the treatment of children with hemophilia. The World Federation of Hemophilia and the World Health Organization have identified preventive treatment as the standard treatment for children with severe hemophilia to prevent bleeding and joint damage, thereby achieving the ultimate treatment goal of preserving normal musculoskeletal function.

8. How do hemophilia patients protect themselves?

Regular inspection

Children with hemophilia should be examined every six months, and adult patients should be examined at least once a year.

Pay attention to oral health

Maintaining good oral hygiene can effectively reduce the occurrence of gum and periodontal diseases, thereby reducing or avoiding some unnecessary dental surgeries.

Choose your medication carefully

Hemophilia patients must pay attention to minimizing intramuscular injections, and it is best to use subcutaneous injections when vaccinating. Aspirin, non-steroidal antipyretic analgesics (such as acetaminophen), and drugs that may affect platelet aggregation are prohibited.

Pay attention to the choice of treatment

Hemophilia patients should try to avoid surgical treatments. If surgical treatment is necessary, they should make perioperative preparations, receive adequate replacement therapy in advance, and may also receive preventive coagulation factor infusions to reduce the occurrence of bleeding and related complications.

Prenatal screening and genetic testing

Although hemophilia patients can get married and have children, there is no effective cure for hemophilia. Therefore, screening and prenatal diagnosis of transmitters can avoid the birth of fetuses with hemophilia and achieve the goal of eugenics.

(Staff from the Henan Institute of Medical Genetics are testing the extracted genes.)

In the past, prenatal testing for hemophilia was mainly done by taking fetal blood through a fetoscopy to measure coagulation factors at 18-21 weeks of pregnancy. However, due to the large individual differences in the level of coagulation factors in the fetus and the certain risks of fetal blood sampling, it is not widely used.

In recent years, due to the rapid development of gene detection technology, the diagnosis of hemophilia carriers and prenatal diagnosis tends to use gene diagnosis methods. It is carried out by extracting and testing peripheral blood and amniotic fluid DNA. It has low risk and high accuracy, and is currently widely used.

Since hemophilia is a relatively rare disease, people are not well aware of it. However, hemophilia is treatable, and patients can work, study, and live like normal people. Therefore, we must understand and pay attention to this disease, and give hemophilia patients more support and care.