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Definition, Description, Causes and symptoms, Diagnosis, Treatment, Prognosis

Hemophilia is a genetic disorder—usually inherited—of the mechanism of blood clotting. Depending on the degree of the disorder present in an individual, excess bleeding may occur only after specific, predictable events (such as surgery, dental procedures, or injury), or occur spontaneously, with no known initiating event.


The normal mechanism for blood clotting is a complex series of events involving the interaction of the injured blood vessel, blood cells (called platelets), and over 20 different proteins which also circulate in the blood.

When a blood vessel is injured in a way that causes bleeding, platelets collect over the injured area, and form a temporary plug to prevent further bleeding. This temporary plug, however, is too disorganized to serve as a long-term solution, so a series of chemical events occur, resulting in the formation of a more reliable plug. The final plug involves tightly woven fibers of a material called fibrin. The production of fibrin requires the interaction of several chemicals, in particular a series of proteins called clotting factors. At least thirteen different clotting factors have been identified.

The clotting cascade, as it is usually called, is the series of events required to form the final fibrin clot. The cascade uses a technique called amplification to rapidly produce the proper sized fibrin clot from the small number of molecules initially activated by the injury.

In hemophilia, certain clotting factors are either decreased in quantity, absent, or improperly formed. Because the clotting cascade uses amplification to rapidly plug up a bleeding area, absence or inactivity of just one clotting factor can greatly increase bleeding time.

Hemophilia A is the most common type of bleeding disorder and involves decreased activity of factor VIII. There are three levels of factor VIII deficiency: severe, moderate, and mild. This classification is based on the percentage of normal factor VIII activity present:

  • Individuals with less than 1% of normal factor VIII activity level have severe hemophilia. Half of all people with hemophilia A fall into this category. Such individuals frequently experience spontaneous bleeding, most frequently into their joints, skin, and muscles. Surgery or trauma can result in life-threatening hemorrhage, and must be carefully managed.
  • Individuals with 1–5% of normal factor VIII activity level have moderate hemophilia, and are at risk for heavy bleeding after seemingly minor traumatic injury.
  • Individuals with 5–40% of normal factor VIII activity level have mild hemophilia, and must prepare carefully for any surgery or dental procedures.

Individuals with hemophilia B have symptoms very similar to those of hemophilia A, but the deficient factor is factor IX. This type of hemophilia is also known as Christmas disease.

Hemophilia C is very rare, and much more mild than hemophilia A or B; it involves factor XI.

Hemophilia A affects between one in 5,000 to one in 10,000 males in most populations.

One recent study estimated the prevalence of hemophilia was 13.4 cases per 100,000 U.S. males (10.5 hemophilia A and 2.9 hemophilia B). By race/ethnicity, the prevalence was 13.2 cases/100,000 among white, 11.0 among African-American, and 11.5 among Hispanic males.

Causes and symptoms

Hemophilia A and B are both caused by a genetic defect present on the X chromosome. (Hemophilia C is inherited in a different fashion.) About 70% of all people with hemophilia A or B inherited the disease. The other 30% develop from a spontaneous genetic mutation.

The following concepts are important to understanding the inheritance of these diseases. All humans have two chromosomes determining their gender: females have XX, males have XY. Because the trait is carried only on the X chromosome, it is called "sex-linked." The chromosome's flawed unit is referred to as the gene.

Both factors VIII and IX are produced by a genetic defect of the X chromosome, so hemophilia A and B are both sex-linked diseases. Because a female child always

Hemophilia A and B are both caused by a genetic defect present on the X chromosome. Approximately 70% of people with hemophilia A or B inherited the disease, while the remaining 30% have hemophilia due to a spontaneous genetic mutation. (Illustration by Electronic Illustrators Group.) Hemophilia A and B are both caused by a genetic defect present on the X chromosome. Approximately 70% of people with hemophilia A or B inherited the disease, while the remaining 30% have hemophilia due to a spontaneous genetic mutation. (Illustration by Electronic Illustrators Group.)

receives two X chromosomes, she nearly always will receive at least one normal X chromosome. Therefore, even if she receives one flawed X chromosome, she will still be capable of producing a sufficient quantity of factors VIII and IX to avoid the symptoms of hemophilia.

Such a person who has one flawed chromosome, but does not actually suffer from the disease, is called a carrier. She carries the flaw that causes hemophilia and can pass it on to her offspring. If, however, she has a son who receives her flawed X chromosome, he will be unable to produce the right quantity of factors VIII or IX, and he will suffer some degree of hemophilia. (Males inherit one X and one Y chromosome, and therefore have only one X chromosome.)

In rare cases, a hemophiliac father and a carrier mother can pass on the right combination of parental chromosomes to result in a hemophiliac female child. This situation, however, is rare. The vast majority of people with either hemophilia A or B are male.

About 30% of all people with hemophilia A or B are the first member of their family to ever have the disease. These individuals have had the unfortunate occurrence of a spontaneous mutation; meaning that in their early development, some random genetic accident befell their X chromosome, resulting in the defect causing hemophilia A or B. Once such a spontaneous genetic mutation takes place, offspring of the affected person can inherit the newly-created, flawed chromosome.

In the case of severe hemophilia, the first bleeding event usually occurs prior to eighteen months of age. In some babies, hemophilia is suspected immediately, when a routine circumcision (removal of the foreskin of the penis) results in unusually heavy bleeding. Toddlers are at particular risk, because they fall frequently, and may bleed into the soft tissue of their arms and legs. These small bleeds result in bruising and noticeable lumps, but don't usually need treatment. As a child becomes more active, bleeding may occur into the muscles; a much more painful and debilitating problem. These muscle bleeds result in pain and pressure on the nerves in the area of the bleed. Damage to nerves can cause numbness and decreased ability to use the injured limb.

Some of the most problematic and frequent bleeds occur into the joints, particularly into the knees and elbows. Repeated bleeding into joints can result in scarring within the joints and permanent deformities. Individuals may develop arthritis in joints that have suffered continued irritation from the presence of blood. Mouth injuries can result in compression of the airway, and, therefore, can be life-threatening. A blow to the head, which might be totally insignificant in a normal individual, can result in bleeding into the skull and brain. Because the skull has no room for expansion, the hemophiliac individual is at risk for brain damage due to blood taking up space and exerting pressure on the delicate brain tissue.

People with hemophilia are at very high risk of hemorrhage (severe, heavy, uncontrollable bleeding) from injuries such as motor vehicle accidents and also from surgery.

Some other rare clotting disorders such as Von Willebrand disease present similar symptoms but are not usually called hemophilia.


Various tests are available to measure, under very carefully controlled conditions, the length of time it takes to produce certain components of the final fibrin clot. Tests called assays can also determine the percentage of factors VIII and IX present compared to normal percentages. This information can help in demonstrating the type of hemophilia present, as well as the severity.

Individuals with a family history of hemophilia may benefit from genetic counseling before deciding to have a baby. Families with a positive history of hemophilia can also have tests done during a pregnancy to determine whether the fetus is a hemophiliac. The test called chorionic villous sampling examines proteins for the defects that lead to hemophilia. This test, which is associated with a 1% risk of miscarriage, can be performed at 10–14 weeks. The test called amniocentesis examines the DNA of fetal cells shed into the amniotic fluid for genetic mutations. Amniocentesis, which is associated with a one in 200 risk of miscarriage, is performed at 15–18 weeks gestation.


The most important thing that individuals with hemophilia can do to prevent complications of this disease is to avoid injury. Those individuals who require dental work or any surgery may need to be pre-treated with an infusion of factor VIII to avoid hemorrhage. Also, hemophiliacs should be vaccinated against hepatitis. Medications or drugs that promote bleeding, such as aspirin, should be avoided.

Various types of factors VIII and IX are available to replace a patient's missing factors. These are administered intravenously (directly into the patient's veins by needle). These factor preparations may be obtained from a single donor, by pooling the donations of as many as thousands of donors, or by laboratory creation through highly advanced genetic techniques.

The frequency of treatment with factors depends on the severity of the individual patient's disease. Patients with relatively mild disease will only require treatment in the event of injury, or to prepare for scheduled surgical or dental procedures. Patients with more severe disease will require regular treatment to avoid spontaneous bleeding.

While appropriate treatment of hemophilia can both decrease suffering and be life-saving, complications associated with treatment can also be quite serious. About 20% of all patients with hemophilia A begin to produce chemicals in their bodies which rapidly destroy infused factor VIII. The presence of such a chemical may greatly hamper efforts to prevent or stop a major hemorrhage.

Individuals who receive factor prepared from pooled donor blood are at risk for serious infections that may be passed through blood. Hepatitis, a severe and potentially fatal viral liver infection, may be contracted from pooled factor preparations. Recently, a good deal of concern has been raised about the possibility of hemophiliacs contracting a fatal slow virus infection of the brain (Creutzfeldt-Jakob disease) from blood products. Unfortunately, pooled factor preparations in the early 1980s were contaminated with human immunodeficiency virus (HIV), the virus which causes AIDS. A large number of hemophiliacs were infected with HIV and some statistics show that HIV is still the leading cause of death among hemophiliacs. Currently, careful methods of donor testing, as well as methods of inactivating viruses present in donated blood, have greatly lowered this risk.

The most exciting new treatments currently being researched involve efforts to transfer new genes to hemophiliacs. These new genes would have the ability to produce the missing factors. As yet, these techniques are not being performed on humans, but there is great hope that eventually this type of gene therapy will be available.


Prognosis is very difficult to generalize. Because there are so many variations in the severity of hemophilia, and because much of what befalls a hemophiliac patient will depend on issues such as physical activity level and accidental injuries, statistics on prognosis are not generally available.



Genetics and Public Health in the 21st Century: Using Genetic Information to Improve Health and Prevent Disease, edited by Muin J. Khoury, Wylie Burke, and Elizabeth J. Thomson. New York: Oxford University Press, 2000.

Hemophilia, edited by C.D. Forbes, L.M. Aledort, and R. Madhok. New York: Chapman & Hall, 1997.

Resnick, Susan. Blood Saga: Hemophilia, AIDS, and the Survival of a Community. Berkeley: University of California Press, 1999.


Soucie, J.M., et al. "Hemophilia Surveillance System Project Investigators: Occurrence of Hemophilia in the United States." American Journal of Hematology 59(1998): 288+.

Stephenson, J. "New Therapies Show Promise for Patients with Leukemia, Hemophilia, and Heart Disease." JAMA 285(January 1, 2001): 153+.


National Hemophilia Foundation. 116 West 32nd St., 11th Floor, New York, NY 10001. (800) 42-HANDI. <http://www.info@hemophilia.org>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or(800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.


National Hemophilia Foundation. 116 West 32nd St., 11th Floor, New York, NY 10001. (800) 42-HANDI. <http://www.info@hemophilia.org>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or(800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.


March of Dimes. <www.modimes.org>.

National Organization for Rare Disorders. <www.rarediseases.org>.

Jennifer F. Wilson, MS


Amplification—A process by which something is made larger. In clotting, only a very few chemicals are released by the initial injury; they result in a cascade of chemical reactions which produces increasingly larger quantities of different chemicals, resulting in an appropriately-sized, strong fibrin clot.

Factors—Coagulation factors are substances in the blood, such as proteins and minerals, that are necessary for clotting. Each clotting substance is designated with roman numerals I through XIII.

Fibrin—The final substance created through the clotting cascade, which provides a strong, reliable plug to prevent further bleeding from the initial injury.

Hemorrhage—Very severe, massive bleeding that is difficult to control. Hemorrhage can occur in hemophiliacs after what would be a relatively minor injury to a person with normal clotting factors.

Mutation—A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted to offspring.

Platelets—Small disc-shaped structures that circulate in the blood stream and participate in blood clotting.


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