Definition of hemophilia – Hemophilia is a blood clotting disorder that is usually inherited. The patients are missing important blood coagulation factors or these are defective. This is why hemophiliacs tend to bleed and “bruise” easily. The hemophilia cannot yet be cured. Thanks to modern therapies, however, hemophiliacs can lead a largely normal life. Read everything you need to know about hemophilia here, such as definition of hemophilia.
ICD codes for this disease: D66 | D67 | D68
Quick overview
• What is hemophilia? A genetic blood clotting disorder (coagulopathy). It is also called hemophilia.
• Types of hemophilia: The most common is hemophilia A, followed by hemophilia B. Other forms such as hemophilia C, von Willebrand-Jürgens syndrome and parahemophilia are less common.
• Causes: Deficiency or defect in coagulation factors (blood proteins that are necessary for the blood to clot). It is usually inherited and only rarely acquired (caused by a spontaneous gene mutation).
• Symptoms: increased tendency to bleed, which leads to bleeding and bruising (hematoma) easily. The bleeding also lasts longer than usual. The severity of the symptoms depends on the severity of the hemophilia.
• Diagnostics: Measurement of various blood parameters (aPTT, Quick value, plasma thrombin time, bleeding time, number of blood platelets), determination of the activity of coagulation factors.
• Treatment: replacement of the missing coagulation factor (in the form of factor concentrates); in certain cases, other drugs (such as desmopressin for mild hemophilia A).
Definition of hemophilia
Haemophilia is a congenital blood clotting disorder. Those affected (“hemophiliacs”) cannot form sufficiently functional coagulation factors. These are proteins in the blood that are necessary for the blood to clot. The lack of coagulation factors means that blood clots cannot form and close wounds as easily. Therefore, hemophiliac patients tend to bleed. In addition, their wounds bleed longer than usual. This can potentially be dangerous.
The medical term for a blood clotting disorder with an increased tendency to bleed is “haemorrhagic diathesis”. The general term for a clotting disorder is “coagulopathy”.
Types of hemophilia
There are different clotting factors. Depending on which coagulation factor is affected in hemophilia, doctors differentiate between different types of the disease.
Hemophilia A
In hemophilia A there are problems with coagulation factor VIII (antihemophilic globulin A): either the body cannot produce it in sufficient quantities, or it is defective. About 85 percent of all hemophiliacs suffer from hemophilia A. Almost all are men.
Hemophilia B
Hemophilia B lacks coagulation factor IX (antihemophilic globulin B or Christmas factor). Here, too, the patients are mostly male. In the past, hemophilia B was common in the English royal family and in the Russian royal family. That is why it is also called the “disease of kings”.
Other types of hemophilia
In addition to the main forms of hemophilia A and B, there are other hereditary coagulation disorders. One of them is Von Willebrand-Jürgens syndrome, also called Von Willebrand syndrome (VWS). The focus here is on the von Willebrand factor: This coagulation factor is either present in too small a quantity or is defective. As with hemophilia A and B, this leads to an increased tendency to bleed (hemorrhagic diathesis). In Europe, Von Willebrand-Jürgens syndrome is found in up to one percent of the population. Unlike the two main forms of hemophilia, this bleeding disorder affects men and women equally.
In rare cases, other coagulation disorders occur that are based on a lack of coagulation factors. They also show an increased tendency to bleed (hemorrhagic diathesis). These include:
• Hemophilia C: lack of functional Factor XI
• Parahemophilia: lack of functional factor V
• Hypoproconvertinaemia: lack of functional Factor VII
• Stuart-Prower Factor Deficiency: Lack of functional Factor X
• Hageman syndrome: lack of functional factor XII
• Fibrinase Deficiency: Lack of functional Factor XIII
Symptoms of hemophilia
The symptoms of hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) are the same – even if different coagulation factors are affected. In general, one can say that the fewer functional coagulation factors are present, the more pronounced the clinical picture.
Hemophilia: degrees of severity
The severity of the hemophilia depends on how much the activity of the clotting factors is reduced compared to their function in healthy people. If the factor activity is only slightly reduced, those affected usually have no symptoms. In contrast, in symptomatic hemophiliacs, factor activity is more reduced, causing more prominent signs. There are three degrees of severity of hemophilia (A and B):
Mild hemophilia : factor activity is 6 to 45 percent of the normal activity of a healthy person; about 20 percent of all people with hemophilia have this degree of severity. Those affected often do not notice much about their illness. For this reason, hemophilia is often not discovered until adolescence or adulthood, when operations or major injuries bleed longer than expected.
Moderate hemophilia : Factor activity is 1 to 5 percent of normal activity; about 20 percent of all hemophiliacs are also affected. The symptoms usually become apparent in the first few years of life with unusually long-lasting bleeding and frequent bruising. As with mild hemophilia, bleeding is usually the result of injury or surgery. Spontaneous bleeding is rare.
Severe hemophilia : Factor activity is less than 1 percent of normal activity. This applies to about 55 percent of all hemophiliacs. The hemophilia usually makes itself felt at birth: removing the umbilical cord triggers massive bleeding. Severe nosebleeds not uncommon in young children. In addition, even the smallest injury or impact can cause severe bleeding under the skin (bruising). Internal bleeding is also more common, for example painful bleeding into the large joints (such as knees, elbows). Typically, many bleeds have no identifiable cause (spontaneous bleeds).
Hemophilia: risks and dangers
Bleeding into the joints (hemarthrosis) often occurs repeatedly, especially in severe hemophilia. As a result, the affected joint can become deformed, wear out prematurely (osteoarthritis) and gradually stiffen. People with advanced hemarthosis can sometimes hardly move their arms and legs and are dependent on a wheelchair.
Another danger associated with hemophilia is bleeding into the muscles : it can damage muscle tissue and lead to muscle weakness.
In principle, internal bleeding in hemophilia can occur in any organ area. Bleeding in the brain is rare but dangerous : for example, it can impair the ability to think and disturb concentration. Severe cerebral hemorrhages can even be life-threatening! Abdominal bleeding can also be life-threatening. Heavy bleeding in the mouth and throat can affect the airways.
In addition to the tendency to bleed (hemorrhagic diathesis), hemophilia of any degree of severity can also lead to wound healing disorders.
Symptoms of Von Willebrand-Jürgens Syndrome
People with Von Willebrand-Jürgens syndrome also have an increased tendency to bleed. In most cases, slight bleeding under the skin (bruising), bleeding gums or prolonged bleeding after surgical interventions, for example after a tooth extraction, occur. But there are also patients who suffer from heavy bleeding.
Treatment of hemophilia
Hemophilia therapy depends on the type and severity of the bleeding disorder. The doctor treating you will create a suitable therapy plan for each patient. In addition to drug treatment, he can also recommend general measures. For example, it may be advisable, especially in the case of severe haemophilia, to take it easy physically and avoid certain (injury-prone) sports.
Hemophilia A and B
Today, so-called factor concentrates are available for the treatment of hemophilia. These are concentrates of blood coagulation factors VIII (for hemophilia A) or IX (for hemophilia B) obtained from blood plasma or genetically engineered. They must be injected into a vein (intravenously). Many sufferers learn to inject themselves with the factor concentrate. This gives them a lot of independence in dealing with the disease.
In the 1960s and 1970s, many people in world contracted hepatitis and/or HIV from contaminated factor preparations. This is practically impossible today: blood plasma is strictly controlled and pre-treated before it is administered. And with genetically engineered factor concentrates there is generally no risk of infection.
In the case of mild and moderate haemophilia, the administration of factor concentrate is only necessary if necessary (on – demand treatment): the anticoagulant is administered, for example, in the event of heavy bleeding or before a planned operation. Minor injuries such as abrasions do not need to be treated with factor concentrate. The bleeding can usually be stopped by applying light pressure to the bleeding area.
People with severe hemophilia, on the other hand, have to inject factor concentrate regularly (long-term treatment). Factor VIII in hemophilia A is given two to three times a week. Factor IX in hemophilia B generally only needs to be injected once or twice a week because it stays in the blood for longer.
Operations and acute injuries
All hemophilia patients must undergo preparatory therapy before operations (even if a tooth is planned to be extracted). A factor concentrate is usually administered for this purpose. This is the only way to prevent serious complications caused by excessive blood loss during the operation.
In the case of mild hemophilia A, a drug that stabilizes blood clotting can be given before a planned operation instead of factor concentrates. This includes, for example, desmopressin. This is an artificially produced protein. It stimulates the release of stored factor VIII from blood vessels. However, the drug can only be used for a few days, otherwise the stores will soon be empty.
Tip: Before a planned procedure, people with hemophilia should discuss with their hematologist or their hemophilia center which preventive therapy is advisable in their case.
In the case of acute injuries in an emergency, in addition to local measures to stop bleeding (e.g. pressure bandage), the administration of factor concentrate is also necessary.
Factor concentrate: complications
Some people form antibodies (inhibitors) against the clotting factors in the factor concentrate. This so-called inhibitor hemophilia is significantly more common in people with hemophilia A than in people with hemophilia B. The inhibitors inactivate the added coagulation factor. The therapy is then not as effective as desired. Hemophilia B can also cause severe allergic reactions and other complications.
The amount of inhibitors in the blood is given in the so-called Bethesda unit (BE). The higher the BE value, the more inhibitors are present in the patient’s blood.
In hemophilia A, mild inhibitor formation can often be compensated for by increasing the dose of factor concentrate. If inhibitors are formed in large quantities, immunotolerance therapy is recommended: The patient receives very high doses of the missing coagulation factor in a complex therapy regimen. The immune system should gradually get used to its presence and stop the formation of inhibitors.
The rare inhibitor hemophilia in hemophilia B is treated differently. For example, those affected receive drugs that affect the immune system (immunomodulators).
Painkiller
A severe bleeding disorder can cause severe pain to those affected. For example, bleeding into the joints can be very painful. Then painkillers like ibuprofen can help. The painkiller acetylsalicylic acid (ASA), on the other hand, is unsuitable for hemophilia: it increases the tendency to bleed even further (a side effect of ASA).
Von Willebrand-Jürgens Syndrome (VWS)
There are different types of Von Willebrand-Jürgens syndrome, which are treated differently: In so-called type 1, the active substance desmopressin is given as needed (before an operation or in the event of acute bleeding). It stimulates the release of stored clotting factors.
Desmopressin is also used in type 2; however, the drug does not always work here. Then the doctor prescribes a factor concentrate (with von Willebrand factor) instead.
Patients with VWS type 3 are always treated with a factor concentrate.
Hemophilia: causes and risk factors
Hemophilia is a congenital genetic disease that is mostly inherited. Rarely, it occurs spontaneously (as a result of a spontaneous gene change = spontaneous mutation).
In hemophiliacs, the genetic information for producing a functional clotting factor is defective: in hemophilia A it is clotting factor VIII, in hemophilia B it is factor IX. The wrong blueprint means that the coagulation factor in question cannot be produced in sufficient, functional quantities. This disrupts blood clotting: wounds do not close as quickly, so bleeding lasts an unusually long time. Spontaneous bleeding (with no apparent cause) also occurs in some patients.
Hemophilia A and B: Heredity
The blueprints (genes) for all parts of the body are located on the chromosomes. There are 46 chromosomes in the cell nucleus of every cell in the body, including two sex chromosomes, which, among other things, determine gender. Females have two X sex chromosomes (XX): one X chromosome was inherited from the mother and one from the father. Males, on the other hand, have a Y chromosome inherited from their father and an X chromosome (XY) inherited from their mother.
The genes for the coagulation factors are on the X chromosome. In women who have two X chromosomes, if one of them contains an incorrect blueprint for a coagulation factor, this can usually be compensated for by the other X chromosome. They are therefore largely symptom-free throughout their lives.
If such a woman has a child, she passes on one of the two X chromosomes to the offspring. There is a 50 percent chance that this is the specimen with the faulty blueprint. By passing on the genetic defect, the mother becomes the carrier of hemophilia. If it is a son, he will be born a bleeder. A daughter, on the other hand, then usually becomes a potential carrier.
In rare cases, the relevant coagulation factor is not formed sufficiently, even in female conductors. Wounds from injuries or operations can then bleed for a long time. It is even rarer for a girl to inherit a faulty X chromosome from both parents. This is usually associated with the hereditary disease Turner syndrome. The affected girls show the full picture of hemophilia.
Von Willebrand-Jürgens Syndrome
In the case of von Willebrand-Jürgens syndrome, the blueprint for the von Willebrand factor (vWF) shows a mutation: the coagulation factor is either insufficient or defective. The gene mutation can occur in both men and women.
Hemophilia: investigations and diagnosis
If someone has frequent spontaneous bleeding (such as nosebleeds) or bruises very easily, this can be a sign of hemophilia. This suspicion is particularly obvious if cases of hemophilia are already known in the family. Those affected should have the increased bleeding tendency clarified by a doctor. The first point of contact if haemophilia is suspected is the general practitioner :
The doctor will first take the patient’s medical history (anamnesis) in a conversation : He will have the symptoms described in detail, ask about any underlying diseases and whether there are known cases of hemophilia in the family.
Laboratory tests are particularly important for clarifying a possible hemophilia. The doctor takes a blood sample from the patient to have it examined in the laboratory for various parameters: In hemophilia, the so-called aPTT (activated partial thromboplastin time) is longer compared to healthy people. On the other hand, the so-called Quick value (thromboplastin time, PT) and the plasma thrombin time (PT) are generally unremarkable; only in severe hemophilia are they prolonged. Also the number of blood platelets (thrombocytes) and the so-called bleeding time are normal in hemophilia A and B. In von Willebrand-Jürgens syndrome, on the other hand, the bleeding time is prolonged. Bleeding time is the amount of time it takes for bleeding to stop.
In order to be able to diagnose hemophilia A or B without a doubt, the activity of the coagulation factors (VIII, IX) must be analyzed. A specialist in hematology or a specialized medical center (hemophilia center) is responsible for this.
Hemophilia: test for newborns and unborn children
If hemophilia has already run in a family, coagulation is usually checked in male newborns immediately after birth. In this way, a bleeding disorder can be detected at an early stage. You can also test for hemophilia during pregnancy.
If a woman suspects that she is genetically predisposed to hemophilia and is therefore a potential carrier, this can be clarified with a genetic test.
Hemophilia: disease course and prognosis
There is currently no cure for hemophilia. Patients have to cope with the lack of coagulation factors throughout their lives. With the help of factor concentrates, however, they can usually lead a largely normal life.
If left untreated, moderate to severe bleeding disorders often lead to serious complications. For example, bleeding into the muscles can cause muscle damage. Bleeding into joints can result in arthrosis and joint stiffness. Such complications can be avoided if hemophilia is recognized early and treated consistently.
