Thursday, July 17, 2008

Hemophilia Disease Information


Hemophilia is an inherited bleeding disorder. Blood contains many proteins, called clotting factors, which work to stop bleeding. People with hemophilia have a low level or absence of one of these clotting factors in their blood.

The lack of clotting factor causes people with hemophilia to bleed for longer periods of time than people whose blood factor levels are normal. People with hemophilia do not bleed faster than other people, and will not bleed to death from a minor cut or injury. The main problem for people with hemophilia is bleeding internally, mainly into muscles and joints.


What is the difference between hemophilia A and hemophilia B?

There are two types of hemophilia: hemophilia A (sometimes called classical hemophilia) and hemophilia B (sometimes called Christmas disease). Both are caused by a low level or absence of one of the proteins in the blood (called factors) that control bleeding. Hemophilia A is caused by a deficiency of factor VIII, and hemophilia B is caused by a deficiency of factor IX.

There is no difference between the two types of hemophilia, except that hemophilia B is about five times less common than hemophilia A.


Are there other types of bleeding disorders?

Yes, there are several other factor deficiencies that also cause abnormal bleeding. These include deficiencies in factors I, II, V, VII, X, XI, XIII and von Willebrand factor. The most severe forms of these deficiencies are even rarer than hemophilia A and B.

von Willebrand disease
Other bleeding disorders


How does a person get hemophilia?

Hemophilia is a genetic disorder, which is usually inherited. It cannot be caught or transmitted except through inheritance. The hemophilia gene is passed down from a parent to a child.

About one third of new cases are caused by a newmutation of the gene in the mother or the child. In these cases, there is no previous history of hemophilia in the family.


Is hemophilia lifelong?

A person born with hemophilia will have it for life. The level of factor VIII or IX in his blood usually stays the same throughout his life.


Does hemophilia only affect men?

The most severe forms of hemophilia affect almost only males. Females can be seriously affected only if the father has hemophilia and the mother is a carrier. This is extremely rare. However, many women who are carriers have symptoms of mild hemophilia.


How is hemophilia inherited?

The hemophilia gene is passed down from a parent to a child.

When the father has hemophilia but the mother does not, none of the sons will have hemophilia. All of the daughters will carry the hemophilia gene.

The genes for hemophilia A and B are on the X chromosome. The chromosomes that determine a person’s sex are called X and Y. Men have an X and a Y chromosome and women have two X chromosomes. Since men have only one X chromosome, if they inherit the hemophilia gene, they will have hemophilia. Because women have two X chromosomes, if one X chromosome has the hemophilia gene, the other X chromosome makes up for it.

Women who have the hemophilia gene are called carriers, and they can pass it on to their children. When the mother is a carrier and the father is normal, for each child there is a 50% chance that a son will have hemophilia and a 50% chance that a daughter will carry the gene. Father with hemophilia Mother carrying hemophilia gene

Are there any precautions a carrier should take if she becomes pregnant?

It is important that a carrier’s hematologist is involved in the supervision of the pregnancy and that there is some liaison with the obstetrician before delivery. It is not necessary to perform prenatal diagnosis just for management of the pregnancy. This is only done if termination of a pregnancy is being considered.

The factor VIII level (but not factor IX) tends to rise during pregnancy but it should bechecked sometime in the last couple of months of pregnancy.

A normal vaginal delivery is perfectly acceptable even if the fetus is known to be male and at risk of hemophilia. Epidural anesthesia does not usually present a problem and is generally permissible if the patient’s factor level is 40 percent or more. A cord blood sample after delivery will be used to check if a male baby has hemophilia.


What is acquired hemophilia?

In rare cases, a person can develop hemophilia later in life. The majority of cases involve middle-aged or elderly people, or young women who have recently given birth or are in the later stages of pregnancy.

Acquired hemophilia is usually caused by the development of antibodies to factor VIII (the body’s immune system destroys its own naturally produced factor VIII).

This condition often resolves with appropriate treatment, which typically involves a combination of steroid treatment and the drug cyclophosphamide.


How common is hemophilia?

Hemophilia is quite rare. About 1 in 10,000 people is born with hemophilia A. About 1 in 50,000 people is born with hemophilia B.


How serious is hemophilia?

The severity of hemophilia is determined by the level of clotting activity of factor VIII or factor IX in the blood. There are three levels of severity: mild, moderate, and severe. The following table shows the range of factor VIII and factor IX activity:
Level
Percentage of normal factor activity in blood
Number of international units (IU) per millilitre (ml) of whole blood

normal range
50%-150%
0.50–1.5 IU

mild hemophilia
5%-40%
0.05–0.40 IU

moderate hemophilia
1%-5%
0.01–0.05 IU

severe hemophilia
less than 1%
less than 0.01 IU


People with severe hemophilia usually bleed frequently into their muscles or joints. They may bleed one to two times per week. Bleeding is often spontaneous, which means the bleeding just happens with no obvious cause.

People with moderate hemophilia bleed less frequently, usually after an injury, perhaps once a month. Cases of hemophilia vary, however, and a person with moderate hemophilia can bleed spontaneously.

People with mild hemophilia usually bleed only as a result of surgery or major injury. They may never have a bleeding problem.


What are the signs of hemophilia?

The signs of hemophilia A and B are the same.
Big bruises
Bleeding into muscles and joints, especially the knees, elbow, and ankles
Spontaneous bleeding (sudden bleeding inside the body for no clear reason)
Bleeding for a long time after getting a cut, removing a tooth, or having surgery
Serious internal bleeding into vital organs, most commonly after a serious trauma


How is hemophilia diagnosed?

Hemophilia is diagnosed by taking a blood sample and measuring the level of factor activity in the blood. Hemophilia A is diagnosed by testing the level of factor VIII coagulation activity in the blood. Hemophilia B is diagnosed by measuring the level of factor IX activity.

If the mother is a carrier, testing can be done before a baby is born. Prenatal diagnosis can be done at 9 to 11 weeks by chorionic villus sampling (CVS) or by fetal blood sampling at a later stage (18 or more weeks).

These tests can be done at a hemophilia treatment centre. A list of treatment centres around the world is accessible from the WFH web site. Click on Passport to search the directory.


Where do bleeds occur?

Most bleeding in hemophilia occurs internally, into the joints or muscles.

The joints that are most often affected are the knee, ankle, and elbow. Repeated bleeding without prompt treatment can damage the cartilage and the bone in a joint, leading to chronic arthritis and disability.

The most serious muscle bleeds are the iliopsoas muscle (the front of the groin area). the forearm, and the calf.

Some bleeds can be life-threatening and require immediate treatment. These include bleeds in the head, throat, gut, or iliopsoas.


How is hemophilia treated?

Hemophilia is treated by replacing the missing clotting factor in the blood. This is done by injecting a product that contains the needed factor into a vein. Bleeding stops when enough clotting factor reaches the bleeding site. It is very important that treatment is given as quickly as possible to prevent long-term damage.

With an adequate quantity of treatment products and proper care, people with hemophilia can live perfectly healthy lives.

Clotting factors are found in the following blood products in order of decreasing concentration:
factor concentrates
cryoprecipitate
plasma
whole blood

Factor concentrates are the treatment of choice for hemophilia. They can be made from human blood (called plasma-derived products) or manufactured using genetically engineered cells that carry a human factor gene (called recombinant products). Factor concentrates are made in sophisticated manufacturing facilities. All commercially prepared factor concentrates are treated to remove or inactivate blood-borne viruses.

People with mild hemophilia A sometimes use desmopressin (also called DDAVP), a synthetic hormone that stimulates the release of factor VIII.

Cryoprecipitate is derived from blood and contains a moderately high concentration of factor VIII (but not IX) clotting factor. It is effective for joint and muscle bleeds, but is less safe from viral contamination than concentrates and is harder to store and administer. Cryoprecipitate can be made at local blood collection facilities.

In fresh plasma the red cells have been removed, leaving the blood proteins including the clotting factors. It is less effective than cryoprecipitate for the treatment of hemophilia A because the factor VIII is less concentrated. Large volumes of plasma must be transfused. This can cause circulatory overload.

The life of the clotting factors is preserved by making a product called fresh frozen plasma (FFP). FFP is still the only product available for treatment of hemophilia A and B in some countries.

There are considerable drawbacks to the use of whole blood in the treatment of hemophilia. First, it must be fresh because the activity of the clotting factors in the drawn blood decreases quickly with time. Second, the red cells it contains must, of course, be compatible with those of the recipient. Third, it takes a large volume of whole blood to stop a bleed and this volume may overload the circulation and cause the heart to fail.


Are bruises dangerous?

Bruises are very common in children with hemophilia. A bruise is not usually cause for alarm unless it is on the person’s head or neck, the person has a hard time moving, the bruise hurts, the lump in the bruise gets larger or does not go away, or there is numbness, or a tingling feeling along with the bruising. If any of these symptoms are experienced, a physician or local hemophilia treatment centre should be consulted.

Should people with hemophilia avoid aspirin?

People with hemophilia should not take aspirin (ASA or acetylsalicyclic acid), or anything containing aspirin, because it interferes with the stickiness of the blood platelets and adds to problems with bleeding.

Paracetamol (acetominophen) is a perfectly safe alternative to aspirin to relieve pain, for example, headaches.


Should people with hemophilia exercise and play sports?

Some people with hemophilia do not exercise because they think it may cause bleeds, but exercise can actually help prevent bleeds. Strong muscles help protect someone who has hemophilia from spontaneous bleeds and joint damage.

Sport is an important activity for young people. It not only helps build their muscles, it helps them develop mental concentration and coordination, and learn about being part of a team. However, some sports are riskier than others, and the benefits must be weighed against the risks. The severity of a person’s hemophilia should also be considered when choosing a sport. Sports like swimming, badminton, cycling, and walking are sports that most people with hemophilia can safely participate in, whilst sports like American football, rugby, and boxing are not recommended for people with hemophilia.

Go for It , a guide to sport for people with hemophilia, can be ordered online using the WFH order form.


What are inhibitors?

Inhibitors are antibodies to factor VIII or factor IX made by the body’s immune system that attack and destroy the factor VIII and IX proteins in clotting factor concentrates, making treatment ineffective. They appear almost exclusively in patients with severe hemophilia. There is some controversy over the precise incidence (number of new cases) of inhibitor development, but it is generally accepted that between 10 and 30 percent of people with severe hemophilia A will develop inhibitors at some stage. By contrast, inhibitor development in hemophilia B is very rare indeed, and seen in 1 to 3 percent of subjects. Most inhibitors emerge after relatively few treatments. In general, the more treatments a person has had without developing inhibitors, the less likely he is to develop an inhibitor.

Treatments exist that can sometimes eliminate inhibitors. In other cases, they disappear naturally. In other cases, they continue for many years.


What is prophylaxis?

Prophylaxis is the regular use of clotting factor concentrates to prevent bleeds before they start. Injections of clotting factor are given one, two or three times a week to maintain a constant level of factor VIII or IX in the bloodstream. Prophylaxis can help reduce or prevent joint damage. In countries with access to adequate quantities of clotting factor concentrates, this is becoming the normal mode of treatment for younger patients, and can be started when the veins are well developed (usually between the ages of two and four years).


What is a venous access device (port-a-cath)?

A port-a-cath, or implantable venous access device (IVAD), is implanted under the skin, usually in the upper chest but there are models which can be inserted into the arm. It has a small metal reservoir with a rubber diaphragm which is connected to a catheter which is then threaded into a large vein in the chest or arm. The entire device is surgically implanted under the skin so there is no catheter that hangs out of the body. The device provides ready access to a vein for administering medications and fluids intravenously. It can also be used for drawing blood samples.

The device is accessed by inserting a special needle through the skin and into the rubber diaphragm of the reservoir. The medication or fluid is injected into the device and it flows through the catheter into the vein.

These devices have made prophylaxis in hemophilia much easier for families because the problems of "finding a vein" for infusion two to three times a week are eliminated. However, there are risks involved with their use, the most worrisome being that of infection. Studies differ but some show an infection rate as high as 50 percent. These infections can usually be treated with intravenous antibiotics but sometimes the device must be removed. Also, there are other studies that show a risk of clots forming at the tip of the catheter. Still, many families have chosen to use the device in spite of the risk because of the benefits. Like any other procedure, one must weigh the risks and benefits.


Is there a cure for hemophilia?

There is no cure for hemophilia yet but gene therapy remains an exciting possibility and holds out the prospect of a partial or complete cure for hemophilia. There are many technical obstacles to overcome, but it is encouraging to see the research efforts currently underway.


What is the life expectancy of someone with hemophilia?

The life expectancy of someone with hemophilia varies depending on whether they receive proper treatment. Without adequate treatment, many people with hemophilia die before they reach adulthood. However, with proper treatment, life expectancy for people with hemophilia is about 10 years less than that of males without hemophilia, and children can look forward to a normal life expectancy.

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