Health Library Should I Have Regularly Scheduled or On-Demand Clotting Factor Replacement Therapy for Hemophilia?From Healthwise

This information will help you understand your choices, whether you share in the decision-making process or rely on your doctor's recommendation.

Key points in making your decision

Consider the following if you have been diagnosed with a moderate to severe form of hemophilia A or hemophilia B and are trying to decide how best to use clotting replacement therapy.

• You likely will have fewer bleeding episodes and a lower risk of serious complications if you use regularly scheduled preventive (prophylactic) therapy. You may be able to participate more freely in activities that might otherwise cause a bleeding injury.
• You will not need treatment as often if you use on-demand clotting replacement therapy. You will be spared some of the cost of and difficulties with injections by waiting until you think you need therapy or until just before you do an activity that might cause a bleeding episode.
• Regularly scheduled therapy will require a steady supply of clotting factor, which is expensive. Most expensive are the clotting factors that are produced in a lab, but these also offer the greatest protection against viral infection.
• When bleeding is suspected, on-demand therapy may not always be practical or feasible. Serious bleeding, such as after a head injury, poses a great danger of bleeding that may be fatal if it is not treated immediately.

A 2002 European study that compared outcomes from on-demand and regularly scheduled treatment reported fewer joint bleeding episodes and better general health in people who received regularly scheduled clotting factor replacement.

What is hemophilia?

Hemophilia is a rare genetic bleeding disorder that almost always occurs in males. A person has hemophilia when he or she inherits problems with certain blood clotting factors, making them unable to work properly. Blood-clotting factors are needed to help stop bleeding after a cut or injury and to prevent spontaneous bleeding.

The hemophilia gene can contain many different errors, leading to different degrees of abnormality in the amount of clotting factor produced. A person with hemophilia often needs treatment to prevent severe 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 deficiency of active clotting factor VIII (8). Approximately 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, occurring in 1 out of every 30,000 male babies.¹

Hemophilia is usually classified by how severe it is. There are three levels of hemophilia, although 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 VIII or clotting factor IX level is 5% of normal or greater. Mild hemophilia might not be recognized unless there is excessive bleeding after a major injury or surgery.
• Moderate hemophilia: Clotting factor VIII or clotting factor IX level is 1% to 5% of normal. Bleeding usually follows a fall, sprain, or strain.
• Severe hemophilia: Clotting factor VIII or clotting factor IX level is less than 1% of normal. Bleeding often happens one or more times a week for no apparent reason (spontaneously).

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 properly because your body makes antibodies that attack them.

What is clotting factor replacement therapy for hemophilia?

Clotting factor concentrates can help control bleeding in people with hemophilia by helping blood to clot properly. They do not cure hemophilia or repair damage that may have already occurred, such as inflammation from repeated episodes of bleeding in the joints. The severity of hemophilia, the location of the bleeding, and how much bleeding has already occurred often determines how much clotting factor concentrate is given.

In the United States, blood products are carefully screened. Blood that is suspected of being contaminated with a virus, such as the human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, is not used. The risk of contracting a virus from donated factor concentrate is very low. But people who receive many units of donated factor concentrate over their lives have a slightly increased risk of being infected with one of these viruses. In addition, hepatitis A virus and parvovirus (the virus that causes fifth disease) are harder to detect and can sometimes be transmitted through donated factor concentrates.

Clotting factor concentrates are not always effective, because the body can develop antibodies called inhibitors, which destroy the newly introduced factor VIII or IX.

What are the main types of clotting factor replacement?

Clotting factor replacement therapy is a way to introduce missing or inadequate amounts of clotting factor VIII or IX components into your blood. Replacing factor VIII will help blood to clot in people who have hemophilia A. Replacing factor IX will help blood to clot in people who have hemophilia B. Clotting factor replacement therapy can be used two ways: on a regularly scheduled basis, to prevent bleeding episodes; or on demand, to prevent or control a bleeding episode that has occurred or is likely to occur.

Clotting factor replacement therapy comes in three main forms: fresh frozen plasma, cryoprecipitate, or factor concentrates.

• Fresh frozen plasma is the liquid part of blood (plasma) taken from a donor and frozen for later use.
  • Fresh frozen plasma contains all types of clotting factors, so it can be used to treat a variety of bleeding problems. It is less expensive than factor concentrates.
  • A large amount of plasma is required to provide enough clotting factor to prevent bleeding. It must be frozen, so it is usually used in a hospital and is not easily kept at home.
• Cryoprecipitate is a blood product that contains all clotting factors, so it can be used to treat many varieties of bleeding disorders.
  • A bleeding episode requires less cryoprecipitate than fresh frozen plasma because cryoprecipitate has been concentrated. Cryoprecipitate is not likely to transmit a disease because it is from only one donor. It is less expensive than donated and recombinant factor concentrates.
  • Although cryoprecipitate is concentrated, a relatively large amount is still required (compared to factor concentrates and recombinant products) to increase clotting factors to a safe level. Cryoprecipitate 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 bleeding episodes that occur outside a hospital.
  • A factor concentrate that is infused on a regular basis can prevent some bleeding episodes from occurring. If you have a factor concentrate infusion soon after a bleeding episode begins, it can prevent bleeding from becoming severe.
  • Clotting factor concentrates are portable, are easily stored, and can be infused at home.
  • Donated factor concentrate is derived from screened blood from many donors and has a high concentration of factor VIII or IX. Donors are carefully screened, and donated blood goes through purifying processes that kill most viruses.
  • Recombinant clotting factors are produced in a lab (using recombinant DNA technology) and are not derived from donated blood. Clotting factors for hemophilia A contain some human or animal proteins, so there is still some risk that they may contain a virus. But the clotting factors produced for hemophilia B do not contain any human or animal products. Recombinant clotting factors are much more expensive than clotting factors made from donated blood.

What are the benefits of regularly scheduled therapy?

You likely will have fewer bleeding episodes, which may be especially important if you have severe hemophilia. You also will have a lower risk of serious complications and long-term damage from repeated bleeding episodes into your muscles or joints.

You may have an improved quality of life. You could more freely participate in activities and exercises that might otherwise cause a bleeding injury.

What are the benefits of on-demand therapy?

On-demand therapy is not needed as often as regularly scheduled treatment, so it is less expensive. Insurance companies are more likely to pay some of the cost.

You will not have to give yourself injections as often.

If a bleeding episode is suspected, prompt on-demand infusions can quickly and effectively control bleeding. You will likely get familiar with your body and be able to tell when a bleeding episode has started, even before you have many symptoms.

Infusions can be given before activities where there is a high risk of bleeding.

What are the risks of regularly scheduled therapy?

Treatment is expensive, especially when clotting factors that are produced in a lab are used. Insurance companies do not always cover the cost of regularly scheduled preventive treatment.

If you use donated clotting factors, you increase your risk of contracting a viral infection.

Usually the infusions must be scheduled 3 times a week, which can disrupt your daily activities. In addition, some people may have a difficult time with the frequent injections.

If you use recombinant clotting factors that are produced in a lab, supplies may not always be available. Shortages are more likely to occur with recombinant clotting factors than with plasma-derived products.

You may increase your risk of developing an inhibitor.

What are the risks of on-demand therapy?

When bleeding is suspected, a quick response may not always be practical or feasible.

If you have severe hemophilia with frequent bleeding episodes, you may not prevent some episodes. As a result, you may develop complications and long-term damage. Also, some children with severe hemophilia who have frequent bleeding episodes miss more school than average, which may cause them to score lower on achievement tests than children who experience fewer bleeding episodes.²

If you have an unexpected accident, it may be difficult to treat a bleeding episode.

Serious bleeding, such as after a head injury, poses a great danger. Head injuries can cause bleeding that may be fatal if they are not treated immediately.

If you need more information, see the topic Hemophilia.

Your choices are:

• Have regularly scheduled blood clotting therapy.
• Have a clotting factor replacement available on demand.

The decision about whether to use regularly scheduled therapy or on-demand therapy takes into account your personal feelings and the medical facts.

These personal stories may help you make your decision.

Use this worksheet to help you make your decision. After completing it, you should have a better idea of how you feel about regularly scheduled and on-demand therapies. Discuss the worksheet with your doctor.

Circle the answer that best applies to you.

Use the following space to list any other important concerns you have about this decision.

What is your overall impression?

Your answers in the above worksheet are meant to give you a general idea of where you stand on this decision. You may have one overriding reason to have on-demand therapy or to have regularly scheduled therapy.

Check the box below that represents your overall impression about your decision.

Return to the topic Hemophilia.

Organizations

Citations

1. Hillman RS, et al. (2005). Hemophilia and other intrinsic pathway defects. In RS Hillman, et al. eds., Hematology in Clinical Practice, 4th ed., chap. 32, pp. 368–379. New York: McGraw-Hill.

2. Shapiro AD, et al. (2001). Defining the impact of hemophilia: The Academic Achievement in Children with Hemophilia study. Pediatrics, 108(6): 1–6.

Author:	Robin Parks, MS	Last Updated: August 20, 2007
Medical Review:	Anne C. Poinier, MD - Internal Medicine Brian Leber, MDCM, FRCPC - Hematology
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