HAEMOPHILIA

What Is Haemophilia?

Haemophilia is a rare inherited bleeding disorder in which the blood does not clot normally. Persons with haemophilia may bleed for a longer time than others after an injury or accident. They also may bleed internally, especially in the joints (knees, ankles, and elbows).

Babies born with haemophilia are missing or have a low level of a protein needed for normal blood clotting or blood coagulation. The protein is called a clotting factor.

Haemophilia usually occurs only in males (with very rare exceptions).

A person with haemophilia has a problem with certain proteins in the blood called clotting factors. Haemophilia can be due to:

• A low level of one of the clotting factors
• A clotting factor that is completely missing

When clotting factors are missing, or your body does not have enough of these factors, it can take a long time for your blood to clot after an injury or accident.

What Is Clotting?

An injury (like a cut) to a blood vessel causes a complex chain of events that results in a blood clot. This clotting process is also called blood coagulation. Clotting is your body's reaction to bleeding and keeps you from losing too much blood. Losing too much blood can be life threatening and can damage your internal organs.

What Is a Clotting Factor?

Clotting factors are proteins in the blood that work with platelets�a type of small blood cell�to help the blood to clot. When blood vessels are damaged, clotting factors help the platelets stick together to plug cuts and breaks at the site of the injury.

In people with haemophilia, blood does not clot as it should because it is missing or has low levels of one of these clotting factors. If blood doesn't clot as quickly or as well as it should, then:

• Heavy blood loss can occur.
• Body organs and tissues can be injured.
• These conditions can result in permanent damage or death.

Sometimes people with haemophilia need infusions of a clotting factor or factors to stop bleeding.

Types of Haemophilia

The two main types of haemophilia are:

• Haemophilia A: Clotting factor VIII (8) is low or missing. About 9 of 10 people with haemophilia have type A.
• Haemophilia B: Clotting factor IX (9) is low or missing.

Haemophilia also can be acquired when antibodies to these clotting factors form and block their function. Only inherited haemophilia is discussed here.

Haemophilia can be:

• Mild
• Moderate
• Severe

Mild, moderate, or severe haemophilia is determined by the amount of clotting factor in the blood. About 7 of 10 people with haemophilia A have the severe form. Normal persons have a factor VIII activity of 100 percent; persons with severe haemophilia A have a factor VIII activity of less than 1 percent.

Other Names for Haemophilia

Haemophilia A

• Classic haemophilia
• Factor VIII deficiency

Haemophilia B

• Christmas disease
• Factor IX deficiency

What Causes Haemophilia?

Haemophilia is an inherited disorder. It is caused by a defect in the genes that determine how the body makes blood clotting factors VIII and IX. These genes are located on the X chromosomes (KRO-muh-somz), which determine whether a baby is a boy or girl.

Chromosomes come in pairs. Females have two X chromosomes, while males have one X and one Y chromosome. A woman is a �carrier� if she has a defective gene for factor VIII or factor IX on one of her X chromosomes. She can pass the defective gene on to her children.

• If she has a son, there is a one in two (50 percent) chance that he will have haemophilia.
• If she has a daughter, there is a one in two (50 percent) chance that the daughter will be a carrier.

A man who has haemophilia cannot pass the disorder on to his sons. All of his daughters, however, will be carriers.

Very rarely, a girl is born with haemophilia. This can happen if her father has haemophilia and her mother is a carrier.

Some males with the disorder are born to mothers who are not carriers. In these cases, a random change (mutation) occurs in the gene as it is passed to the child.

What Are the Signs and Symptoms of Haemophilia?

The major signs and symptoms of haemophilia are:

• Bleeding
• Bruising

Internal bleeding is common in people with severe haemophilia. If not treated promptly, internal bleeding can lead to damaged joints, muscles, or other parts of the body.

The extent of bleeding depends on the type and severity of the condition:

• Children with very mild haemophilia may not have noticeable symptoms for years. Often, the first sign is heavy bleeding from a dental procedure, an accident, or surgery.
• Children with mild to moderate haemophilia may not have any signs or symptoms at birth.
• Males with severe haemophilia may bleed heavily after circumcision.

In most children, the first signs are:

• Heavy bruising and bleeding from the gums as they cut their baby teeth
• Bumps and bruises from frequent falls as they learn to walk
• Swelling and bruising from bleeding in the joints, soft tissue, and muscles

Females who are carriers usually have enough clotting factors from their one normal gene to prevent serious bleeding problems.

The most common signs or symptoms in older children and adults are:

• Bleeding in the joints (hemarthrosis (HE-mar-thro-sis))
• Bleeding and bruising in the soft tissue and muscles
• Bleeding in the mouth from a cut or bite or loss of a tooth
• Nosebleeds for no obvious reason
• Blood in the urine (from bleeding in the kidneys or bladder)
• Blood in the stool (from bleeding in the intestines or stomach)

Bleeding in the joints is the most common problem in persons with severe haemophilia. Bleeding often occurs without an injury. It can go on for days if not treated. However, people with haemophilia can learn to recognise early symptoms of bleeding in the joints and get treatment quickly. Early treatment can help limit damage to the joints.

Although bleeding can occur in any joint, the most common places are the:

• Knees
• Elbows
• Ankles

The signs and symptoms of bleeding in the joints are:

• Tightness in the joint with no real pain is usually the first sign.
• Tightness and pain may occur before any visible signs of bleeding.
• The joint becomes swollen and hot to touch as time passes. Bending or extending the joint is painful.
• Swelling continues as bleeding continues, and all movement in the joint is lost. Pain can be severe.
• The bleeding slows after several days when the joint is full of blood.

If not treated, the bleeding can lead to disabling arthritis in the joints.

Bleeding in the brain, a very serious complication of haemophilia, requires emergency treatment. This bleeding can happen after a simple bump on the head or a more serious injury. The signs and symptoms are:

• Long-lasting painful headaches
• Vomiting many times
• Changes in behaviour or being very sleepy
• Sudden weakness or clumsiness of the arm or leg
• Neck pain or stiffness
• Double vision
• Difficulty walking
• Convulsions or seizures

How Is Haemophilia Diagnosed?

If haemophilia is suspected or if you appear to have a bleeding problem, your doctor will take a personal and family history, do a physical exam, and order blood tests.

Blood tests are used to determine:

• How long it takes for your blood to clot
• Whether your blood has low levels of any of the clotting factors
• Whether one of the factors is completely missing from your blood

The test results will show if you have haemophilia, what type of haemophilia you have, and how severe it is.

Haemophilia A and B are classified as mild, moderate, or severe, depending on the amount of clotting factor VIII (8) or IX (9) in the blood.

Mild haemophilia	>5�30 percent of normal factor
Moderate haemophilia	1�5 percent of normal factor
Severe haemophilia	Less than 1 percent of normal factor

Severe haemophilia can cause serious bleeding problems in babies. Therefore, children with severe haemophilia are usually diagnosed during the first year of life. People with milder forms of haemophilia may not be diagnosed until they are adults.

The bleeding problems of haemophilia A and haemophilia B are the same. These two types of haemophilia can only be distinguished by special blood tests. Distinguishing haemophilia A from haemophilia B is important because the treatments are different.

How Is Haemophilia Treated?

The main treatment for haemophilia is �replacement therapy��giving or replacing the clotting factor that is too low or missing. Concentrates of the clotting factor are infused, or injected, directly into the bloodstream. The specific factors used to treat haemophilia are:

• Factor VIII for haemophilia A
• Factor IX for haemophilia B

Replacement therapy can be used:

• To prevent bleeding (prophylactic (PRO-fih-lac-tik) or preventive therapy)
• To stop bleeding when it occurs, on an as-needed basis (demand therapy)

The type of treatment you receive depends on several things, including whether you have mild, moderate, or severe haemophilia.

• Mild haemophilia. Replacement therapy is usually not needed for mild haemophilia; however, a medicine called desmopressin (DDAVP) is sometimes given to raise the body's levels of factor VIII. Since the effect wears off with chronic use, it is applied only in certain situations (for example, prior to dental work or participation in sports) to prevent or reduce bleeding. Desmopressin does not help in haemophilia B.
• Moderate haemophilia. You may need treatment only when bleeding occurs. You will need to learn to recognise signs and symptoms of bleeding so that you can get treatment as quickly as possible. You may also have treatment to prevent bleeding that could occur when participating in some activity.
• Severe haemophilia. You usually need long-term or shorter term preventive therapy to prevent bleeding that could cause permanent damage to your joints, muscles, or other parts of the body. Some people with severe haemophilia receive treatment only when bleeding occurs, however.

When bleeding occurs, it is important to get treatment as soon as possible. Delayed treatment can lead to complications. Learn to recognise signs of bleeding, and make sure that it is treated quickly.

Sources of Clotting Factors

The clotting factor concentrates used in replacement therapy come from two sources:

• Blood from human donors
• Lab-produced clotting factors, called recombinant (reh-COM-bih-nant) factors, that are not made from human blood

Clotting factors from either source are safe. However, recombinant factors cannot carry viruses and are usually preferred for treating haemophilia. Recombinant clotting factors work the same as natural clotting factors in blood. Infusions need to be given once daily or more frequently when treatment is started, because half of the activity of factor VIII is gone in 8�12 hours and half of the activity of factor IX is gone in 12�24 hours.

Clotting factors used in replacement therapy today are:

• Very powerful�only a small amount is needed to control bleeding.
• Easy to store, mix, and use at home�it takes only about 15 minutes to receive the factor.

Replacement Therapy To Prevent Bleeding

Replacement therapy can be given on a regular basis to prevent bleeding. The goal is to keep the levels of clotting factors in the blood high enough that bleeding will not occur.

This therapy is more likely to be used in persons with severe haemophilia. It is often used in children to prevent damage to joints from bleeding.

Preventive replacement therapy can be given:

• On a long-term basis, usually given two or three times a week
• On a shorter term basis, such as over a few months
• On a short-term basis before participating in an activity that could cause bleeding

This therapy can be intensive and expensive. Preventive therapy is often given at home.

Replacement Therapy To Stop Bleeding When It Occurs

Replacement therapy can be given as needed, or on demand, to stop bleeding as soon as possible after it begins. The goal is to prevent damage to joints, muscles, or other parts of the body from bleeding. This therapy is common for people with mild or moderate haemophilia.

The amount of clotting factor given depends on:

• The type of haemophilia
• The bleeding site and severity of the bleeding
• The person's weight
• Whether the person has developed an antibody that neutralizes or knocks out the activity of the clotting factor

Therapy that is given as needed is less intensive and less expensive than regular preventive therapy. However, there is a risk that bleeding will cause damage before the treatment is given.

People who use this form of treatment must learn to recognise bleeding when it occurs. Treatment must begin right away to limit damage. Family members should also learn to watch for signs of bleeding in a child. Children sometimes ignore signs of bleeding because they want to avoid the discomfort of treatment.

Complications of Replacement Therapy

Complications of treatment include:

• Developing antibodies, which are proteins that knock out the activity of clotting factors
• Damage to joints, muscles, or other parts of the body, resulting from delays in treatment

Antibodies to the clotting factor

Antibodies destroy the clotting factor before it has a chance to work. This is a very serious problem, because the main treatment for haemophilia�replacing clotting factors�is no longer effective.

Antibodies to clotting factor develop in about:

• Twenty percent of people with severe haemophilia A
• One percent of people with haemophilia B

When antibodies develop, doctors may use larger doses of clotting factors or try different sources of the clotting factor. Sometimes, antibodies go away. Researchers are studying ways to deal with antibodies to clotting factors.

Viruses from human blood factors

The viruses that cause AIDS (HIV) and hepatitis can be carried in clotting factors. However, no documented case of transmission of these viruses has occurred for about a decade. Transmission of viruses has been prevented by:

• Careful screening of donors
• Testing of donated blood products
• Treating donated blood products, used to create clotting factors, with a detergent and heat to destroy viruses

Researchers continue to find ways to make blood products safer.

Damage due to delays in treatment

When treatment for bleeding is delayed, damage to the area affected (such as a joint) can occur. It is important for persons with haemophilia to learn to recognise signs of bleeding as soon as possible after bleeding starts and to get treatment quickly.

Home Treatment

Both preventive and as-needed therapy can be done at home. Many people learn to do the infusions at home for their child or for themselves. Home treatment has several advantages:

• You or your child can get treatment quicker when bleeding happens. Early treatment means that fewer complications are likely to occur.
• Fewer visits to the doctor or emergency room are needed.
• Home infusions cost less than treatment in a medical care setting.
• Home treatment helps children accept treatment and take responsibility for their own health.

Discuss options for home treatment with your doctor or your child's doctor. A doctor or other health care provider can teach you the steps and safety procedures for home treatment. Another valuable resource for learning about home treatment is through haemophilia treatment centers (HTCs) (see below).

Vein access devices can be surgically implanted to make it easier to access a vein to do the infusions. These devices can be helpful when infusions are done on a frequent basis. However, infections can be a problem with these devices. Your doctor can help you decide if this type of device is right for you or your child.

Other Treatments

Desmopressin

Desmopressin (DDAVP) is a synthetic hormone used to treat people with mild to moderate haemophilia A. DDAVP cannot be used to treat haemophilia B or severe haemophilia A. DDAVP stimulates the release of factor VIII and von Willebrand factor stored in blood vessels and increases the level of these proteins in the blood. Von Willebrand factor carries and binds factor VIII, which then can stay in the blood circulation longer. DDAVP usually is given by injection or in a nasal spray.

Antifibrinolytic drugs

Antifibrinolytic drugs (including tranexamic acid and aminocaproic acid) are medicines used with factor treatment. They are usually given as a pill to help keep clots from breaking down. They are most often used:

• Before dental work
• For treating bleeding from the mouth or nose
• For mild intestinal bleeding

What To Expect

If your child has severe haemophilia, you and your family will have things to cope with and adjustments to make:

• After diagnosis
• As your child grows and becomes more active
• As your child becomes a teenager

Expect emotional, financial, social, and other strains as you adjust to the situation. It is important to learn all you can about the disorder and get the support you need:

• Talk with doctors and other health care providers about treatment, prevention of bleeding, and what to do in emergencies.
• The care teams at the HTCs are excellent resources for education and support as well as treatment. The social worker on the team can help with emotional issues, financial and transportation problems, and other concerns.
• Many resources are available through the Web, and books and other materials are available from national and local haemophilia organisations.
• Look into support groups that offer a variety of activities for children with haemophilia and for family members. Some groups offer summer camps for children with haemophilia.

Ongoing Medical Care Needs

To avoid complications, it is important that those with haemophilia:

• Continue any treatment prescribed for haemophilia.
• Get regular checkups and immunizations as recommended. Children with haemophilia normally get the same immunizations as other children but not as intramuscular injections. Vaccines for hepatitis A and B are recommended for those who are treated with blood transfusions. There is currently no vaccine for hepatitis C.
• Get regular dental care. Dentists at the HTCs are experts in providing dental care for those with haemophilia. If you see another dentist, tell the dentist that you have or your child has haemophilia. You or your child can receive medicine that reduces bleeding before having dental work.
• Know the signs of bleeding in joints and other parts of the body and when to call the doctor or go to the emergency room.

Contact your doctor or go to the emergency room for:

• Heavy bleeding that cannot be stopped or a wound that continues to ooze blood.
• Any symptoms of bleeding in the brain; this situation is life threatening and requires immediate emergency care.
• Limited motion, pain, or swelling of any joint.

It is a good idea to keep a record of all previous treatments. Be sure to take this information with you to medical appointments and to the hospital or emergency room.

Haemophilia in Childhood

Challenges occur as your child grows and becomes more active. In addition to treatment and regular health and dental care, including immunizations, your child needs:

• A safe environment at home, at daycare, at school, or at the babysitter's
• A healthy diet to help maintain a healthy weight for his or her size
• Education about the child's condition in a way he or she can understand
• Support in dealing with having chronic health considerations
• Reassurance that having haemophilia is not his or her fault

Young children need protection from things in the home and elsewhere that could cause injuries and lead to bleeding. Here are some tips:

• Protect your toddler with kneepads, elbow pads, and protective helmets. All children should wear safety helmets when riding tricycles or bicycles and should use the proper car seats or seat belts when riding in a car.
• Be sure to use the safety belts and straps in highchairs, car seats, and strollers to protect your child from falls.
• Remove furniture with sharp corners or pad them while your child is a toddler.
• Keep out of reach or locked away small and sharp objects and other items that could cause bleeding or harm your child.
• Use cabinet locks to prevent your child from opening cabinets.
• Use electrical outlet covers.
• Use baby security gates to keep your child away from stairs and other areas where he or she could fall or be injured.
• Check play equipment and outdoor play areas for possible hazards.
• Keep a cold pack in the freezer ready to use as directed or to take along with you to treat bumps and bruises. Popsicles work fine when there is minor bleeding in the mouth.
• Keep a bag ready to go with items you will need if you must take your child to the emergency room or elsewhere.
• Be sure that anyone who is responsible for your child knows that the child has haemophilia. Talk with your child's babysitters, daycare providers, teachers, other school staff, and coaches or leaders of afterschool activities about when to contact you or to call 9�1�1 for emergency care.
• Consider having your child wear a medical ID bracelet or necklace. If your child is injured, the ID will alert anyone caring for your child about the condition.
• Learn how to examine your child for and recognise signs of bleeding.

Haemophilia in Adolescence

Adolescence can be a difficult time for both the teenager and the family. Having to cope with haemophilia can be an added stress. As your child begins to take more responsibility for himself and his treatment, he will need education, supervision, and support.

Teenagers can learn to:

• Recognise signs of bleeding and take appropriate action
• Keep a diary or record of treatment
• Do home infusions for themselves (with supervision)
• Exercise regularly and safely
• Avoid taking unnecessary risks
• Take care of teeth and gums
• Eat a healthy diet

Physcial Activity and Haemophilia

Physical activity helps keep muscles flexible, strengthens joints, and helps in maintaining a healthy weight. Children and adults with haemophilia should get regular physical activity, but they may have restrictions on what they can do safely.

People with mild haemophilia can participate in a variety of activities. Those with severe haemophilia should avoid contact sports and other activities that are likely to lead to injuries that could cause bleeding.

The physical therapist at the HTC can develop an exercise programme tailored to your needs and teach you how to exercise safely. Talk with your doctor or physical therapist about recommended types of physical activity and sports.

To prevent bleeding, you or your child also may be able to take clotting factor prior to exercise or a sporting event.

In general, some safe physical activities are:

• Swimming
• Biking (wearing a helmet)
• Walking
• Golf

Activities that are not usually considered safe for those with bleeding problems include most contact sports, such as:

• Football
• Hockey
• Wrestling

Medication Precautions

Some medicines thin your blood and increase the chance for bleeding. You should avoid medicines such as:

• Aspirin and other drugs that contain salicylates (sa-LIH-sil-ates); never give any child medicine that contains aspirin.
• Ibuprofen (EYE-boo-pro-fen).
• Other nonsteroidal anti-inflammatory drugs, such as naproxen.

Treatment at Home and When travelling

Home treatment has many benefits. It allows:

• Early treatment of bleeding
• Fewer trips to the hospital
• More independence
• A sense of control over the disorder

If you are treating yourself with infusions of clotting factors, or treating your child at home, you should take some precautions:

• Follow recommendations for storage, preparation, and use of clotting factors and treatment materials.
• Keep a record of all medical treatment.
• Know the signs and symptoms of bleeding or infection and what to do.
• Have someone with you when you do your infusions.
• Know the signs and symptoms of an allergic reaction and what to do.
• Know when to call the doctor or 9�1�1.

When travelling:

• Take adequate treatment materials along. Make sure to take enough clotting factors for the length of the travel.
• Get a letter from your doctor or your child's doctor describing your condition or your child's condition and treatment. Always carry the doctor's letter with you when travelling.
• Find out in advance where to go for care when out of town.

Cost Issues

Clotting factors are very costly, and many health insurance companies will only pay for clotting factors on a case-by-case basis. It is important to know:

• What your insurance covers
• Whether your insurance has a limit on the dollar amount it will cover and what that amount is
• Whether there are restrictions or waiting periods

As children grow, it is important to learn about available options for insurance. Career counselling can help you or your child find a job and keep health insurance coverage.

Education and Job Training

If you have haemophilia, it is important that you complete your education. Getting a good education and advanced job training �opens the door� to the kinds of jobs that are ideal for those who cannot do hard physical work.

Key Points

• Haemophilia is a rare inherited bleeding disorder.
• About 400 babies are born with haemophilia each year in the United States. Haemophilia almost always occurs in males.
• A baby born with haemophilia has a problem with certain proteins in the blood, called clotting factors, which help blood clot. Haemophilia can be due to a low level of one of these clotting factors or due to a clotting factor that is completely missing.
• When clotting factors are missing, or your body does not have enough of these factors, it can take a long time for your blood to clot after an injury or accident. Bleeding often occurs internally.
• There are two main types of haemophilia: A and B. People with haemophilia A have low levels of clotting factor VIII or are missing it altogether. People with haemophilia B have low levels of clotting factor IX or are missing it altogether.
• Haemophilia is caused by a defect in the genes that determine how the body makes certain blood-clotting factors. The genes are located on the X chromosomes that determine whether a baby is a boy or girl.
• The major signs and symptoms of haemophilia are bleeding and bruising. The extent depends on the type and severity of the condition.
• Bleeding often occurs internally, such as in joints and muscles. If bleeding in the brain occurs, it is a medical emergency.
• To diagnose haemophilia, your doctor will take a personal and family history, do a physical exam, and order blood tests. The tests will show if you have a bleeding problem, if it is due to haemophilia or another cause, and how severe the disorder is.
• The main treatment for haemophilia is injecting the low or missing clotting factors directly into the bloodstream. This is called replacement therapy.
• Replacement therapy sometimes can be given on a long-term basis to prevent bleeding. Those persons with severe haemophilia are more likely to receive this type of preventive replacement therapy.
• Replacement therapy can be given on demand (as needed) to stop bleeding when it occurs. This therapy is more common for those with milder haemophilia.
• Early treatment for bleeding is important to prevent or limit damage to joints, muscles, or other parts of the body.
• Replacement therapy is often done at home. Home treatment has many benefits, but it is important to be trained to do home infusions properly and safely.
• Exercise is important for children and adults. Talk with your doctor about the type of exercise that is best for you or for your child and what to do to prevent injuries.
• If you have or your child has haemophilia, learn as much as you can about the disorder. If possible, join a support group.