Hemophilia: Should I Have Regularly Scheduled or On-Demand Clotting Factor Replacement?

Hemophilia is a rare genetic bleeding disorder that almost always occurs in men. People who have hemophilia have clotting factors that don't work correctly. Blood-clotting factors are needed to help stop bleeding after a cut or injury and to prevent bleeding that happens for no clear reason. A person with hemophilia often needs treatment to prevent blood loss and stop internal bleeding.

There are two major types of hemophilia, although the symptoms are the same.

• Hemophilia A is caused by a lack of active clotting factor VIII (8). About 1 out of every 5,000 male babies is born with hemophilia A.¹
• Hemophilia B (Christmas disease) is caused by a lack of active clotting factor IX (9). It is less common, and occurs in 1 out of every 30,000 male babies.¹

Hemophilia is usually labeled by how severe it is. There are three levels of hemophilia, but they can overlap. The severity of the disease is defined by how much clotting factor is produced and in what situations bleeding most often occurs.

• Mild hemophilia: Clotting factor level is 5% of normal or greater. Mild hemophilia might not be recognized unless there is a lot of bleeding after a major injury or surgery.
• Moderate hemophilia: Clotting factor level is 1% to 5% of normal. Bleeding usually follows a fall, sprain, or strain.
• Severe hemophilia: Clotting factor level is less than 1% of normal. Bleeding often happens one or more times a week for no clear reason.

The percentage of clotting factors stays about the same throughout a person's life. All family members who have hemophilia usually will have similar forms.

In very rare cases, a person develops a form of hemophilia, called acquired hemophilia, that is not inherited. If you have acquired hemophilia, your clotting factors don't work right because your body makes antibodies that attack them or stop them from working the way they should.

Clotting factor replacement is a way to replace missing amounts of clotting factor in your blood. When you have hemophilia, you can inject doses of clotting factor concentrates to help your blood to clot. Clotting factors come from donated blood or are produced in a lab as a powder form that you mix with sterile water and inject into your veins.

How much clotting factor you need depends on how bad your hemophilia is, where the bleeding is, and how much bleeding you have already had.

Clotting factor replacement can be done in one of two ways:

• On a regularly scheduled basis, to prevent bleeding problems, or
• On demand, to prevent or control a bleeding problem that has happened or is about to happen

Clotting factor replacement doesn't cure hemophilia or fix damage that has already happened, such as swelling from repeated problems with bleeding in the joints.

In the United States, blood products are carefully tested. If there is a chance that donated blood has been infected with a virus, such as HIV, hepatitis B, or hepatitis C, it is not used.

The risk of getting a virus from donated clotting factor is very low. But people who receive many units of donated blood factor concentrate over their lives have a slightly increased risk of getting one of these viruses. Plus, hepatitis A and parvovirus (the virus that causes fifth disease) are harder to detect than these other viruses. They can sometimes be spread by donated blood. If you use clotting factor that is made in a lab, also called a recombinant clotting factor, you have almost no risk of getting an infection.

There are three main types of clotting factor replacement:

• Fresh frozen plasma is the liquid part of blood (plasma) taken from a donor and frozen for later use.
  • Frozen plasma has all types of clotting factors, so it can be used to treat many different bleeding problems. It costs less than other kinds of clotting factor.
  • A lot of plasma is needed to provide enough clotting factor to prevent bleeds. It must be frozen. It's usually used in a hospital and is not easily kept at home.
• Cryoprecipitate is a blood product that has many clotting factors, so it can also be used to treat many kinds of bleeding problems.
  • It is concentrated, so you need less of it than you would of frozen plasma to stop a bleed. But you need more of it than you do of other types of factor concentrates, including the kind made in a lab, to raise clotting factors to a safe level.
  • It's not likely to spread a virus, because it comes from only one donor. It costs less than other types of concentrated clotting factor.
  • It must be frozen, so it is usually used in a hospital and is not easily kept at home.
• Factor concentrates are used to prevent or treat bleeds that happen outside a hospital.
  • If you give yourself (infuse) factor concentrate on a regular basis, you can prevent some bleeds from happening. And if you infuse soon after a bleed begins, you can stop the bleed before it gets bad.
  • You can carry factor concentrates with you. They are easily stored and can be infused at home.
  • Donated factor concentrate comes from blood from many donors and has a high level of clotting factor. Donors are carefully screened. Donated blood is purified to kill most viruses.
  • Clotting factors that are made in a lab, also called recombinant clotting factors, do not come from donated blood. Clotting factors for hemophilia A carry a slight risk of containing a virus. But the clotting factors produced for hemophilia B do not have this risk. Clotting factors made in a lab cost much more than factors made from donated blood.

You likely will have fewer bleeds if you get clotting factor on a regular schedule. This is especially important if you have severe hemophilia. You will also have a lower risk of problems linked to bleeding, such as long-term damage from repeated bleeding into your muscles or joints.

On-demand treatment is not needed as often as scheduled treatment, so it costs less. Health insurers are more likely to pay some of the cost.

You won't have to give yourself injections of clotting factor as often as you would with scheduled treatment. You would do it only as needed.

If you think that you are having a bleeding problem, on-demand treatment can quickly control bleeding. You will likely get to know your body and be able to tell when a bleed has started, even before you have many symptoms.

You can give yourself a shot before you begin activities where there is a high risk of bleeding.

Treatment is costly, and health insurers don't always cover the cost of this preventive treatment. If you use clotting factor that is made in a lab, it may cost even more, and supplies may not always be available.

If you use donated clotting factors, you increase your risk of getting an infection.

Usually injections must be scheduled 3 times a week. This can get in the way of your daily life. Some people may have a hard time giving themselves shots that often.

You may increase your risk of your body making antibodies (called inhibitors) that attack the clotting factors you are getting for treatment. People who develop these inhibitors need other treatment.

When bleeding is suspected, you may not always be able to act quickly.

If your hemophilia is severe and you often have bleeds, you may not be able to prevent some bleeding problems. You might have long-term damage and start to have other health problems.

If you have a sudden accident, it may be hard to treat a bleed. Serious bleeding, such as after a head injury, can be fatal if it is not treated right away.