Hemophilia

Signs and Symptoms

Hemophilia A and B are caused by genetic mutations in the gene for factor VIII or factor IX. Mutations are abnormal changes that occur in a gene. The gene for factor VIII and factor IX is located on the X chromosome, making Hemophila A and B X-linked disorders. As such, one copy of the abnormal factor VIII or factor IX gene results in hemophilia in males, and a carrier state in females. When there is a family history of hemophilia, the mother usually is a carrier and half of her sons and some of her male relatives will have hemophilia. If there is no family history of hemophilia, the disorder is due to a new mutation that occurred either in the affected individual, or in the individual's mother, whose carrier state may have gone unnoticed.

The most common symptom of hemophilia is bleeding, particularly into the joints and muscles. When a person with hemophilia is injured, he does not bleed faster than a person without hemophilia, but it takes longer for bleeding to stop. Bleeding also may start again several days after an injury or surgery. Small cuts or surface bruises usually are not a problem, but deeper injuries may result in bleeding episodes that can lead to permanent disability unless they are treated promptly.

Other symptoms of hemophilia include easy bruising, prolonged nosebleeds, or vomiting of blood.

Hemophilia may occur in mild, moderate and severe forms, based on both clinical symptoms and the level or amount of clotting factor in the blood.

• An individual with mild hemophilia has 6 percent to 49 percent of the normal factor level, and usually bleeds only after serious injury, trauma or surgery. The first episode of bleeding may not occur until adulthood.
• An individual with moderate hemophilia has 1 percent to 5 percent of the normal factor level and has bleeding episodes after injuries, major trauma or surgery. He also may experience occasional bleeding without obvious cause, called spontaneous bleeding episodes.
• An individual with severe hemophilia has less than 1 percent factor level and experiences bleeding following an injury or surgery, and may have frequent spontaneous bleeding episodes into the joints and muscles.

A person's severity of hemophilia does not change over time because factor level is determined by genetics. If a person cannot make clotting factor when he is young, he will never have the ability to make clotting factor.

Diagnosis

Accurate diagnosis is essential for the optimal management of hemophilia. Testing for hemophilia should be performed at a highly experienced specialized coagulation laboratory, such as at UCSF Medical Center. Laboratories that do not frequently perform these specialized tests may not be able to accurately establish a diagnosis.

Most people with hemophilia are diagnosed at an early age. However, those with mild hemophilia may not be diagnosed until adulthood when they experience a bleeding episode due to trauma or surgery.

The diagnosis of hemophilia is made by blood tests to determine if clotting factors are missing or at low levels, and which ones are causing the problem. If you have a family history of hemophilia, it is important that your doctors know the clotting factor your relatives are missing, since you will probably be missing the same one.

If you know you are a carrier of hemophilia, the testing for hemophilia in your newborn usually occurs soon after birth. These tests can be run on blood obtained from the umbilical cord or drawn from the newborn's vein. You may be advised to delay some procedures, such as circumcision, until after you learn whether your child has hemophilia.

Some families with a history of hemophilia may want to request prenatal testing, or testing before birth. This testing can be done early in pregnancy, allowing your family to make informed decisions and preparations. UCSF Children's Hospital has genetic counselors who are available to help you with prenatal testing, if desired.

If you are pregnant and think you could be a carrier, or if you have a child diagnosed with hemophilia and you are expecting another child, it is important that you tell your obstetrician that you are at risk for having a child with hemophilia. There are three ways to determine if you are a carrier:

• Family Tree -- If you have a son with hemophilia and have another son, brother, father, uncle, cousin or grandfather with the disorder, then you are an obligate carrier. No additional tests are needed.
• Clotting Factor -- Measure clotting factor level in your blood. If it is below 50 percent of normal, you probably are a carrier and have mild hemophilia. If the clotting factor level is above 50 percent, you still may be a carrier, since other conditions can elevate the factor level. Other tests may be necessary.
• DNA Test -- Conduct a DNA test to look for the mutation that caused hemophilia in your son or another relative, and compare it to your DNA. It is necessary to obtain samples of blood from your son or relative with hemophilia.

Treatment

Our health care team can help you decide which is the best treatment option for you. We rely on your input to help develop a plan of care that will keep you healthy, active and able to live successfully with the challenges of hemophilia.

The present goal of hemophilia therapy is to raise factor levels, decrease the frequency and severity of bleeding episodes and prevent complications of bleeding with the use of clotting factor concentrates. Clotting factor concentrate, also called "factor," is a dried powder form of the clotting factor. It is mixed with water to form a liquid before it is given. Some clotting factor products, called plasma-derived factor products, are made from donated human blood plasma. Others, called recombinant factor products, are made in a laboratory and do not use human blood proteins. Recombinant factor products are safer since they decrease the potential transmission of viruses from donated blood.

Clotting factor concentrate is injected into your vein soon after you have had an injury or show signs of bleeding. When clotting factor is given, it immediately circulates in the blood so the body can use it immediately to form a blood clot. Once the blood clot is established and the bleeding has stopped, the body begins to reabsorb the blood that has leaked into the tissues and joints.

If you do not receive prompt treatment, extra blood can pool in the joint or soft tissue and cause pain and swelling that takes longer to go away. Over time, repeated bleeding into a joint can lead to severe joint damage and arthritis. Early treatment will minimize the risk of joint damage.

If you have mild hemophilia, you may only need to be treated episodically, that is, each time you experience a bleeding episode. If your hemophilia is moderate or severe, your hemophilia may require more frequent treatment.

Home Therapy

All factor treatments are infused or injected intravenously into a vein. At first, you will be treated at a hemophilia treatment center, your doctor's office or an emergency room. Later, you may be taught how to administer the factor at home. Devices, called ports, can be surgically inserted under the skin in the chest area to make it easier to administer clotting factor products.

Whether or not you are on home treatment, you should always have factor concentrate at home, since you may need to take it to the emergency room when you need a treatment. If the decision is made to infuse factor to treat your bleeding episode, the most important thing you can do is to administer it as soon as possible. If there is a delay, however, you can apply ice to help shrink the size of the leaking blood vessels, limit the amount of bleeding into joints or tissues and prevent a small bleed from becoming a larger one. To avoid ice burn, place a cloth, such as a washcloth, between the ice and your skin.

After you receive factor treatment for a joint bleed, rest, ice, compression and elevation (or "RICE") are required. You may also benefit from support devices, such as crutches, following a bleed into the knee or ankle, or a sling, following a bleed into a muscle or joint in the arm. Depending on the site of the bleed, you may have to limit activities for a few days after a bleed.

Over-the-Counter Medications

Acetaminophen, sold under the brand names Tempra and Tylenol, is recommended as a safe pain reliever for people with hemophilia. Follow the directions carefully and be sure to take only the recommended amount of the medicine.

Never take any product with aspirin, or acetylsalicylic acid, in it. Aspirin can interfere with clotting. Many common household remedies, such as Alka-Seltzer, contain aspirin, so read labels very carefully before you take any medication. Ibuprofen, such as Advil, Aleve and Motrin, also may interfere with clotting; these should be used only if you have discussed their side effects with your doctor If you have any questions about what is or is not safe for you to take, talk to your doctor or hemophilia medical staff.

Experimental Treatments

Although safe recombinant clotting factors now allow people with hemophilia to live a long, full life, researchers are still attempting to find a cure for the disease. Technically, hemophilia can be cured through a liver transplant, but the risks involved in the surgery and the requirement for lifelong medications to prevent rejection of the new liver may outweigh the benefits.

Researchers also are currently working on a way to insert a normal copy of the factor VIII or factor IX gene into the cells of patients with hemophilia to raise factor levels enough to decrease the frequency and severity of bleeding episodes and to prevent the complications of bleeding. So far, these approaches have not led to long-term increases in factor level, but it is hoped that they will be effective in the future.