hemophilia

Quick Overview

• What is hemophilia? A genetic coagulation disorder (coagulopathy). It is also called hemophilia.
• Forms of hemophilia: Hemophilia A is the most common, followed by hemophilia B. Rarer are other forms such as hemophilia C, von Willebrand-Jürgens syndrome and parahemophilia.
• Reason: Deficiency or deficiency of coagulation factors (blood proteins that are necessary for the blood to coagulate). He is usually inherited and rarely acquired (caused by a spontaneous gene mutation).
• symptoms: Increased tendency to bleed, which can easily lead to bleeding and bruising (hematoma). The bleeding also lasts longer than usual. The severity of the symptoms depends on the severity of the hemophilia.
• Diagnosis: Measurement of various blood parameters (aPTT, Quick value, plasma thrombin time, bleeding time, number of 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 medications (such as desmopressin in mild hemophilia A)

Hemophilia: description

Haemophilia is a congenital disorder of blood clotting. The affected persons (blood patients, “hemophiliacs”) can not form sufficiently functional coagulation factors. These are proteins in the blood that are necessary for the blood to coagulate. Due to the lack of coagulation factors, blood clots can not easily form and seal wounds. Therefore hemophilia patients are prone to bleeding. In addition, wounds bleed longer than usual. This can be dangerous under certain circumstances.

The medical term for a blood clotting disorder with increased bleeding tendency is “hemorrhagic diathesis”. The common name for a coagulation disorder is “coagulopathy”.

Hemophilia: frequency

Hemophilia occurs almost exclusively in boys or men. It is relatively rare: only about two out of every 10,000 men have hemophilia. In Germany there are about 10,000 affected people. About 3,000 to 5,000 of them suffer from a severe form of the disease.

Hemophilia: forms

There are different coagulation factors. Depending on which coagulation factor is affected in hemophilia, medics differentiate different forms of the disease.

Hemophilia A

In hemophilia A, there are problems with the Coagulation factor VIII (Antihemophilic Globulin A): Either the body can not produce it in sufficient quantity, or it is defective. About 85 percent of all people with blood disorders suffer from haemophilia A. Almost all of them are men.

Hemophilia B

Hemophilia B is missing Coagulation factor IX (Antihemophilic Globulin B or Christmas factor). Again, the patients are mostly male. In the past, haemophilia B frequently occurred in the English royal family as well as in the Russian tsar family. That is why it is called the “sickness of kings”.

Other forms of hemophilia

In addition to the main forms of hemophilia A and B, there are other hereditary coagulation disorders. One of them is that von Willebrand syndrome, also called von Willebrand syndrome (vWS). The focus here is the von Willebrand factor: This coagulation factor is either present in too small amount or defective. This leads – as in hemophilia A and B – to an increased bleeding tendency (hemorrhagic diathesis). In Germany, von Willebrand-Jürgens syndrome is found in up to one percent of the population. Unlike the two main forms of hemophilia, this coagulation disorder affects men and women alike.

In rare cases, other coagulation disorders occur due to a lack of coagulation factors. They also show an increased bleeding tendency (haemorrhagic diathesis). They include:

• Hemophilia C: Lack of functional factor XI
• Para hemophilia: Lack of functional factor V
• hypoproconvertinemia: Lack of functional factor VII
• Factor X deficiency: Lack of functional factor X
• Hageman syndrome: Lack of functional factor XII
• Fibrinase deficiency: Lack of functional factor XIII

Hemophilia: symptoms

The symptoms at 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 less functional coagulation factors are present, the more pronounced is the clinical picture.

Hemophilia: severity

The severity of hemophilia depends on how much the activity of the coagulation factors is diminished compared to their function in healthy people. If the factor activity is only slightly reduced, sufferers usually have no complaints. In contrast, in symptomatic hemophiliacs, factor activity is more reduced, causing more obvious signs. There are three degrees of hemophilia (A and B):

Mild hemophilia:The 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 severity. The affected people often do not notice much of their illness. Therefore, hemophilia is discovered in many people only at adolescence or adulthood when surgery or major injury bleeds for longer than expected.

Moderate hemophilia: The factor activity is 1 to 5 percent of the normal activity; About 20 percent of all hemophiles are affected as well. The complaints are usually evident in the first 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: The factor activity is less than 1 percent of the normal activity. That applies to about 55 percent of all hemophiliacs. The hemophilia is usually noticeable at birth: The removal of the umbilical cord triggers a massive bleeding. In infancy heavy nosebleeds are not uncommon. In addition, even the smallest injuries or bumps cause heavy bleeding under the skin (bruising). Internal bleeding also occurs more frequently, for example painful bleeding in the large joints (such as knees, elbows). Typically, many bleeds have no apparent cause (spontaneous bleeding).

Hemophilia: risks and dangers

Especially in severe hemophilia often occur repeatedly Bleeding in the joints (Hemarthrosis) on. As a result, the affected joint may deform, premature wear (osteoarthritis) and gradually stiffen. People with advanced hemarthrosis can sometimes move their arms and legs and rely on a wheelchair.

Another danger in hemophilia are Bleeding into the muscles: They can damage muscle tissue and lead to muscle weakness.

In principle, internal haemophilia bleeding can occur in any organ area. Rare, but dangerous Bleeding in the brainThey can, for example, affect the mind and disturb the concentration. In severe cerebral hemorrhage is even mortal danger! Also Bleeding in the abdominal area can be life threatening. Strength Bleeding in the mouth and throat area can affect the respiratory system.

In addition, in hemophilia of any severity, in addition to bleeding tendency (haemorrhagic diathesis), it may also increase wound healing come.

Von Willebrand-Jürgens syndrome: symptoms

People with von Willebrand-Jürgens syndrome also have an increased tendency to bleed. Most of the time, mild bleeding under the skin (bruising), bleeding gums, or prolonged bleeding after surgery, for example, after a tooth extraction. But there are also patients who suffer from heavy bleeding.

Hemophilia: treatment

Hemophilia therapy depends on the type and severity of the hemophilia. The attending physician will create a suitable treatment plan for each patient. In addition to the drug treatment, he can still recommend general measures. For example, it may be advisable, especially in severe hemophilia, to spare oneself physically and to renounce certain (injury) sports.

Hemophilia A and B

Today, so-called hemophilia treatment is available factor concentrates to disposal. These are blood plasma derived or genetically engineered concentrates of the coagulation factors VIII (for hemophilia A) or IX (for hemophilia B). They have to be injected into a vein (intravenously). Many sufferers learn to inject the factor concentrate themselves. As a result, they gain a lot of independence in dealing with the disease.

In the 1960s and 1970s, many people in Germany were infected by contaminated factor preparations with hepatitis and / or HIV. This practically can not happen today: blood plasma is strictly controlled and pretreated before it is administered. And genetically engineered factor concentrates are generally not contagious.

at mild and moderate haemophilia is the administration of factor concentrate only necessary if necessary (need treatment): The anticoagulant is given in case of a major bleeding or before a planned operation. Minor injuries such as abrasions need not be treated with factor concentrate. The bleeding can usually be stopped by applying light pressure to the bleeding area.

People with one severe hemophilia on the other hand, factor concentrates have to be sprayed regularly (Maintenance treatment). The factor VIII in hemophilia A is administered two to three times a week. Hemophilia B Factor IX generally only needs to be injected once or twice a week because of its prolonged retention in the blood.

Surgery and acute injuries

Prior to surgery (even with planned tooth extraction), all haemophilia patients must have one preparatory therapy be performed. For this purpose, usually a factor concentrate is administered. This is the only way to prevent serious complications from excessive blood loss during surgery.

In mild hemophilia A, a drug that stabilizes blood coagulation may be given instead of factor concentrates prior to planned surgery. This includes about desmopressin, This is an artificially produced protein. It stimulates the release of stored factor VIII from blood vessels. 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 what preventive therapy is advisable in their case.

For acute injuries in case of emergency, in addition to local measures of hemostasis (for example compression bandage) the administration of factor concentrate is also necessary.

Factor concentrate: complications

Some people make antibodies (inhibitors) against the coagulation 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. Haemophilia B also causes severe allergic reactions and other complications.

The amount of inhibitors in the blood is indicated 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 Often, mild inhibitor formation can be compensated for by increasing the dose of factor concentrate. When inhibitors are formed in larger quantities, immune tolerance therapy is recommended: the patient receives very high doses of the missing coagulation factor in a complex regimen. So 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 hemophilia can cause severe pain to those affected. For example, bleeding into the joints can be very painful. Then help painkillers such as ibuprofen. On the other hand, the analgesic acetylsalicylic acid (ASA) is unsuitable for hemophilia: it further enhances the tendency to bleed even further (side effect of ASA).

Von Willebrand-Jürgens syndrome (VWS)

In von Willebrand-Jürgens syndrome, a distinction is made between different types, which are treated differently: In the so-called type 1, the active substance desmopressin is given if necessary (before surgery or in acute bleeding). It stimulates the release of stored coagulation factors.

Type 2 also uses desmopressin; However, the drug does not always work here. Then the doctor will instead prescribe a factor concentrate (with von Willebrand Factor).

Patients with the VWS type 3 are always treated with a factor concentrate.

Hemophilia: causes and risk factors

Hemophilia is an inherited genetic disease that is usually inherited. It rarely occurs spontaneously (as a result of a spontaneous gene change = spontaneous mutation).

In haemophilia, the genetic information for producing a functional coagulation factor is flawed: hemophilia A is coagulation factor VIII, hemophilia B is factor IX. The wrong plan has the consequence that the clotting factor in question can not be produced in a sufficiently functional amount. This interferes with blood clotting: wounds do not close so quickly that bleeding lasts unusually long. Some patients also experience spontaneous bleeding (with no apparent cause).

Hemophilia A and B: heredity

The blueprints (genes) for all body components lie on the chromosomes. In the cell nucleus of each body cell one finds 46 chromosomes, under it two sex chromosomes, which among other things determine the sex. Women have two X sex chromosomes (XX): One X chromosome each was inherited from the mother and the father. Men, on the other hand, have a father-inherited Y chromosome and an X-derived X chromosome (XY).

The genes for the coagulation factors are located on the X chromosome. If in women who have two X chromosomes, one of them contains a faulty blueprint for a coagulation factor, this can usually be compensated by the other X chromosome. As a result, they are largely symptomless throughout their lives.

If such a woman receives a child, she passes on one of the two X chromosomes to the offspring. The probability that this is the copy with the faulty blueprint is 50 percent. By passing on the genetic defect, the mother becomes Carrier (Conductor) hemophilia. If it is a son, this is born as a bleeding. A daughter, on the other hand, usually becomes a potential conductor in turn.

In rare cases, the coagulation factor in question is not adequately formed even in the case of female conductors. Wounds resulting from injury or surgery can then bleed longer. Even more rarely does a girl inherit a faulty X chromosome from both parents. This is then usually in conjunction with the hereditary disease Turner syndrome. The affected girls show the full picture of hemophilia.

Von-Von Willebrand disease

In Von Willebrand-Jurgens syndrome, the construction manual of von Willebrand factor (vWF) has a mutation: The coagulation factor is present in too small an amount or is defective. The gene mutation can occur in both men and women.

Hemophilia: examinations and diagnosis

If someone often gets spontaneous bleeding (such as nosebleeds) or bruising very easily, it may be an indication of hemophilia. This suspicion is especially obvious when cases of hemophilia are already known in the family. Patients should have the increased bleeding tendency checked out by a doctor. The first contact for suspected hemophilia is the family doctor:

The physician is first talking to the patient To raise medical history (Anamnesis): He describes the symptoms accurately, asks about possible underlying diseases and whether cases of haemophilia in the family are known.

Especially important for the clarification of a possible hemophilia are laboratory tests, The doctor takes a blood sample from the patient to have them examined for various parameters in the laboratory aPTT (activated partial thromboplastin time) compared to healthy prolonged. On the other hand, the so-called Quick value (Thromboplastin time, TPZ) and the plasma thrombin (PTZ) generally unremarkable; only in severe hemophilia they are prolonged. Also the number of platelets (platelets) 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 time it takes for bleeding to stop.

To determine hemophilia A or B unequivocally, the Activity of coagulation factors (VIII, IX) are analyzed. There is one for that Specialist in hematology or a specialized medical center (hemophilia center).

Hemophilia: test in neonates and unborn children

If hemophilia has already occurred in a family, coagulation in male newborns is usually checked immediately after birth. This is how a hemophilia can be detected early. Even during pregnancy, you can already check for hemophilia.

If a woman suspects that she has the genetic predisposition to haemophilia and is thus a potential carrier, this can be verified by a genetic test.

Hemophilia: disease course and prognosis

Hemophilia is not curable so far. 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 and severe hemophilia often lead to serious complications. For example, bleeding into the muscles can cause muscle damage. Joint bleeding can cause osteoarthritis and joint stiffness. Such complications can be avoided if one hemophilia recognized early and treated consistently.