Hemophilia



Hemophilia 2351
Photo by: Leah-Anne Thompson

Hemophilia (he-mo-FIL-e-a) is a hereditary disorder in which the blood does not clot normally and excessive bleeding results.

KEYWORDS

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Bleeding disorders

Blood transfusion

Clotting factors

Coagulation disorders

Fibrin

Hematology

Most people take certain bodily functions for granted: breathing, digestion, healing. We do not have to think about them; they just happen. Blood clotting is one of these things—at least it usually is. But for the approximately 20,000 people in the United States with hemophilia A or B, a simple thing like losing a tooth or falling off a bicycle can cause life-threatening complications. This is because their blood does not clot, or coagulate, normally. And without clotting, any injury will just continue to bleed.

What Is Hemophilia?

Hemophilia is an inherited deficiency of a blood-clotting factor that results in excessive bleeding. When a healthy person is injured, a sequence of events occurs to cause the blood to turn from liquid to solid (a clot) and to stop flowing. First, platelets (tiny capsule-shaped cells in the blood) begin to stick together and form a small plug at the point of bleeding. Platelets contain an enzyme, or protein, that causes fibrinogen (fy-BRIN-o-jen), a substance in the blood, to change to fibrin (FY-brin), a hard substance that does not dissolve. Like firemen racing to a burning building, fibrin rushes to the area of blood vessel injury and piles up, helping the platelets to block the opening and stop the blood flow.

Fibrin can perform this task only by using substances in the blood manufactured by the body called clotting factors. The clotting factors are numbered I through XIII. In hemophilia A, clotting factor VIII is deficient. Factors I through VII function properly, but then the clotting

The gene for hemophilia is unintentionally passed from mothers (XX) to sons (XY) via the X chromosome. A son who inherits a defective X chromosome from his mother does not have a healthy X chromosome to rely on the way daughters (XX) do.
The gene for hemophilia is unintentionally passed from mothers (XX) to sons (XY) via the X chromosome. A son who inherits a defective X chromosome from his mother does not have a healthy X chromosome to rely on the way daughters (XX) do.
process is interrupted and blood from a wound continues to flow. Hemophilia B, which occurs less frequently, is caused by a deficiency of factor IX. Sending fibrin to clot blood without these factors is like sending firemen to a fire without enough water to put it out.

Hemophilia varies in severity. Most healthy people have 100 percent levels of clotting factor VIII or IX in their blood. In contrast, people with the most severe forms of hemophilia have less than 1 percent of the normal amount. Unable to clot blood at all, they can begin to hemorrhage, or bleed internally, even without external injuries.

Those with moderate hemophilia have factor VIII or IX levels between 1 and 5 percent. Excessive bleeding follows minor injury as well as dental extractions and surgeries. Mild hemophilia is seen in those with factor VIII or IX levels between 6 and 50 percent. For this group, excessive bleeding is usually associated only with major injuries, surgical procedures, or tooth extractions. People with mild cases may not be diagnosed as having hemophilia until adulthood, when unexplained and excessive bleeding accompanies an operation or a visit to the dentist.

What Causes Hemophilia?

Hemophilia is not contagious like a cold or flu. It is usually inherited, which means that it often runs in families. Hemophilia almost exclusively affects boys. It is caused by a defective gene that is unintentionally passed from mothers to sons via the X chromosome.

Usually, female "carriers" have normal levels of clotting factors themselves. If a man with hemophilia marries a woman who is a carrier, there is a possibility of having a daughter with hemophilia, but this is rare. Up to one third of the people with hemophilia have no family members who have the condition or who are carriers. In these cases, a mutation (a change in a gene) has produced a new hemophilia gene, which may be passed on to following generations.

How Do People Know They Have Hemophilia?

Although hemophilia is present at birth, babies who are not circumcised (a surgical procedure to remove the foreskin of the penis) seldom experience problems until they begin to crawl. Once they start to bump into hard surfaces or fall, they begin to bleed into muscles or joints, places where two bones meet. Such internal bleeding can cause joints to bruise and swell painfully.

Joint bleeding is serious, because it can lead to arthritis (inflammation of the joints), deformity, and disability. Prompt treatment is necessary to prevent severe pain and swelling. As boys with hemophilia grow older, they often learn to recognize joint bleeding before the pain or swelling appears as a "funny," tingling feeling.

What Are Chromosomes and Genes?

A chromosome is a paired, thread-like structure found in the nucleus or central, controlling part of the body's cells that determines the development of characteristics for each individual person. The one obvious characteristic to be determined is whether a person is male or female. A female has two X chromosomes, and a male has one X and one Y.

Chromosomes are composed of genes, units that determine everything from the color of eyes to how a body functions. The X chromosome carries genes that control the production of clotting factors VIII and IX. In people with hemophilia, these genes cause the body to produce too little VIII or IX. But even if a woman (XX) has one X chromosome with the hemophilia gene, the other X chromosome is probably normal, and her body will produce enough factor VIII or IX to ensure that the blood will clot. The Y chromosome, however, has no part in the production of blood-clotting factors. Boys (XY) who inherit a defective X chromosome from their mothers have no other X chromosome to fall back on to prevent them from having hemophilia.

Bleeding into a muscle, most often the calf, thigh, or forearm, commonly occurs after injury; sometimes this occurs spontaneously. The resulting swelling, which may develop over several days, may create pressure inside the muscles and damage nerves and blood vessels. Symptoms include muscle tightness, pain, skin temperature change, and tingling or numbness. Early treatment is needed to prevent paralysis or permanent immobility.

HIV and Hemophilia

One of the greatest risks faced by those with hemophilia in the late 1970s and early 1980s was the possibility of contracting HIV, the AIDS virus. This happened when people got transfusions of clotting factors drawn from infected blood. It is estimated that 55 percent of people with hemophilia were infected with HIV in this way between 1979 and 1985.

In those days, blood donations were not tested for HIV. And people with hemophilia were especially likely to get infected for two reasons: They got many transfusions and each transfusion contained pooled clotting factors drawn from the blood of many, many donors in order to get enough clotting factors to be effective. If any one of those donors was infected with HIV, the person with hemophilia was at risk.

Today, however, the blood supply is much safer. Potential blood donors are screened to eliminate those who might have been exposed to HIV, and all blood is tested for the virus. These measures apply to all blood transfusions. In addition, clotting factors drawn from blood are treated with heat and other virus-killing techniques, although these methods are not used for other kinds of transfusions because they can damage other blood products.

The safety measures produced dramatic results. From 1986 to 1999, according to the National Hemophilia Foundation, no one with hemophilia contracted HIV from a transfusion in the United States. Now new technology allows clotting factors to be genetically engineered without the use of blood donations.

European Royalty and Hemophilia

History's most famous carrier of the gene for hemophilia was Victoria (1819-1901), Queen of England and grandmother to most of the royalty in Europe. In 1853, Queen Victoria gave birth to her eighth child, Leopold, Duke of Albany, who had hemophilia and died at the age of 31 from internal bleeding after a fall.

Two of Queen Victoria's four daughters, Alice (b. 1843) and Beatrice (b. 1857), also carried the gene for hemophilia and subsequently transmitted the disease to three of Victoria's grandsons and to six of her great-grandsons.

Alice's daughter Alexandra also was a carrier of hemophilia, and she transmitted the disease to her son Alexis (b. 1904), whose father was Czar Nicholas 11 (1868—1918) of Russia. Alexis is perhaps the most famous of the European royals with hemophilia. Alexis was the heir to his father's throne and his medical condition caused much anxiety in the royal household. Historians are still discussing the role Alexis's condition played in the Russian revolution of 1918.

Czar Nicholas II of Russia and his family, photographed c. 1916, showing his wife Alexandra (who was a carrier of hemophilia), his four daughters, and (in the foreground) his son Alexis, perhaps the most famous European royal with hemophilia. Corbis.
Czar Nicholas II of Russia and his family, photographed c. 1916, showing his wife Alexandra (who was a carrier of hemophilia), his four daughters, and (in the foreground) his son Alexis, perhaps the most famous European royal with hemophilia.
Corbis.

Any type of neck or head injury can be extremely dangerous for anyone with hemophilia. Neck and throat hemorrhages can obstruct breathing. Head injury, even a minor fall or bump on the head, can cause bleeding into the brain; the symptoms include irritability, headache, confusion, nausea, vomiting, and double vision.

People with hemophilia bruise very easily, but skin bruises are rarely serious. Bleeding from small cuts and scrapes can usually be stopped by applying firm pressure to the area for several minutes. Deep cuts, on the other hand, can bleed profusely and require treatment.

Clotting factors are transfused through the vein, often at a hospital or doctor's office. With proper training, people with hemophilia or their parents can perform transfusions at home. © SIU/Visuals Unlimited.
Clotting factors are transfused through the vein, often at a hospital or doctor's office. With proper training, people with hemophilia or their parents can perform transfusions at home.
© SIU/Visuals Unlimited.

Diagnosis

Using DNA testing (direct analysis of the genes), it is possible to determine whether a woman is a "carrier" of the hemophilia gene. Blood tests can measure the level of clotting factors in the blood. Tests can be performed on fetuses to see if they have inherited hemophilia.

Treatment

People with hemophilia often need to be given the blood-clotting factors they lack. These factors may be drawn from the blood donations of many people and purified. Or, since the mid-1990s, they may be produced by genetic engineering, which does not require blood donations. The clotting factors are transfused through the person's vein, often at a hospital or doctor's office. With proper training, a person can perform transfusions at home, or parents can do it for their children.

One medication that should not be used by those with hemophilia is aspirin, a pain reliever, since it interferes with normal blood clotting and increases people's tendency to bleed.

How often transfusions are needed depends on how severe the illness is and how often the person gets injured. In cases of major injury or surgery, a person may need transfusions two or three times a day for days or weeks. Even without being injured, some people with severe hemophilia may get transfusions on a regular basis to prevent problems. People with mild cases of hemophilia may rarely or never need transfusions.

A medication called DDAVP (desmopressin), which is not a blood product, can sometimes help to release any extra factor VIII stores in people with mild or moderate hemophilia A. This temporary treatment may help a person avoid a transfusion after a minor injury, for instance.

Prevention of Bleeding Episodes

As soon as a child is diagnosed with hemophilia, parents should try to prevent or reduce the occurrence of bleeding. Doctors recommend choosing soft toys without sharp corners and padded clothing—particularly at the elbows and knees—while a child is learning to walk. Children should be immunized, but the injections should be given under the skin rather than into the muscles to prevent hemorrhages. Children should also be taught to clean their teeth regularly and to visit the dentist to prevent tooth decay and gum disease.

Did You Know?

  • Hemophilia A occurs in about one out of every 5,000 male births; hemophilia B in about one out of every 30,000.
  • The average person with hemophilia infuses 80,000 to 100,000 units of blood-clotting factor a year.
  • Care for a typical severe hemophilia patient costs $100,000 to $150,000 per year.
  • Severe hemophilia accounts for 60 percent of all those with the disease.

Living with Hemophilia

Hemophilia is usually not a fatal disorder, and people with hemophilia often live long and active lives. Activities such as swimming, walking, and bicycling can help build up muscles that support the joints. Contact sports such as football or wrestling, however, are prohibited because of the high risk of head or neck injury.

Explaining hemophilia to friends and family can help boys feel less self-conscious about their condition and educate others about the importance of prompt treatment.

The Future

At present, there is no cure for hemophilia, but trials with gene therapy are under way. Many of them are concentrating on replacing the gene that causes hemophilia with a normal one that will raise the level of deficient clotting factors to promote coagulation.

Other researchers have produced genetically engineered animal cells into which they have inserted the genetic sequence to produce human factor VIII.

See also
AIDS and HIV
Clotting
Genetic Diseases
Hemorrhage

Resources

Books and Magazines

White, Ryan, and Anne Marie Cunningham. Ryan White: My Own Story. Signet, 1992.

Hemalog. A quarterly magazine for people with bleeding disorders.

Organizations

National Hemophilia Foundation
http://www.infonhf.org/

World Foundation of Hemophilia
http://www.wfh.org/



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