Hemophilia is a coagulation disorder arising from a genetic defect of the X chromosome; the defect can either be inherited or result from spontaneous gene mutation. In each type of hemophilia (hemophilias A, B, and C), a critical coagulation protein is missing, causing individuals to bleed for long periods of time before clotting occurs. Depending on the degree of the disorder in the affected individual, uncontrolled bleeding may occur spontaneously with no known initiating event, or occur after specific events such as surgery, dental procedures, immunizations, or injury.
The body's normal mechanism for blood clotting is a complex series of events (coagulation cascade) involving interaction between the injured blood vessel, blood cells called platelets, 13 specific coagulation factors (designated by Roman numerals I through XIII), and other substances that circulate in the blood.
When blood vessels are injured in a way that causes bleeding, platelets collect over the injured area, forming 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 occurs that results in the formation of a more reliable plug. The final plug or clot involves tightly woven fibers of a material called fibrin. The production of fibrin requires the interaction of a series of proteins, clotting factors I through XIII, in a process called amplification to rapidly produce the proper-sized fibrin clot from the small number of molecules initially activated by the injury. In the complex coagulation process, the absence or inactivity of just one clotting factor can greatly increase bleeding time. In hemophilia, certain clotting factors are either decreased in quantity, absent altogether, or improperly formed, preventing the formation of a clot and resulting in uncontrolled bleeding.
Hemophilia A is the most common type of coagulation 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 percent 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 musculoskeletal bleeding into their joints, skin, and muscles. Surgery or trauma can result in life-threatening hemorrhage and must be carefully managed.
- Individuals with 1–5 percent of normal factor VIII activity level have moderate hemophilia and are at risk for heavy bleeding after seemingly minor traumatic injuries.
- Individuals with 5–40 percent of normal factor VIII activity level have mild hemophilia and must prepare carefully for any surgery or dental procedures.
In hemophilia B, or Christmas disease, the deficient clotting factor is factor IX, but the symptoms are very similar to those of hemophilia A. Factor IX is produced in the liver and is dependent on interaction with vitamin K in order to function properly. A deficiency in vitamin K can affect the clotting factor's performance as well as a deficiency in the factor itself.
Hemophilia C is rare and much milder than hemophilia A or B. It involves reduced activity of factor XI and is characterized by mild bleeding such as nosebleeds (epistaxis) or prolonged menstrual bleeding, or mild bleeding after tonsillectomies or dental extractions.
Hemophilia A affects between one in 5,000 to one in 10,000 males in most populations. Hemophilia B occurs in one in 40,000 to 50,000. The prevalence of hemophilia is estimated to be 13.4 cases per 100,000 U.S. males (10.5 hemophilia A and 2.9 hemophilia B). By race/ethnicity, the prevalence is 13.2 cases in 100,000 among white males, 11.0 among African-American males, and 11.5 among Hispanic males. Hemophilia C occurs primarily among individuals of Jewish descent.
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 percent of all people with hemophilia A or B inherited the disease. The other 30 percent develop from a spontaneous genetic mutation.
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 passed on from a female to male offspring. (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.) Because a female child always receives two X chromosomes, she will nearly always 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. However, the vast majority of people with either hemophilia A or B are male.
About 30 percent 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 affected their X chromosome, resulting in the defect that causes 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 18 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 do not usually require treatment. As a child becomes more active, bleeding may occur into the muscles, a much more painful and debilitating situation. 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.
Christmas disease varies from mild to severe, but mild cases are more common. The severity depends on the degree of deficiency of factor IX. Hemophilia B symptoms are similar to those of hemophilia A, including numerous large and deep bruises and prolonged bleeding.
Some of the most problematic and frequent bleeds occur into the joints, particularly 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, which interrupts breathing and can be life-threatening. A blow to the head, which might be totally insignificant in a normal child, can result in bleeding into the skull and brain. Because the skull has no room for expansion, the hemophiliac 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 severe, heavy, uncontrollable bleeding (hemorrhage) from injuries such as motor vehicle accidents and also from surgery.
Some other rare clotting disorders such as von Willebrand's disease present similar symptoms but are not usually called hemophilia.
When to call the doctor
Hemophilia is usually discovered when an injury initiates bleeding and the bleeding will not stop. In very young children, spontaneous musculoskeletal bleeding may occur around the time the child begins to walk; these episodes may be the first sign of hemophilia. In some children, a simple surgical procedure, such as a tooth extraction or injection, may present with uncontrolled bleeding. Any signs of deep bruises or the presence of prolonged bleeding after a bump or an injury that breaks the skin should be reported to a physician or emergency service immediately. Bleeding under the skin (hematoma), which looks like a severe bruise, should also be reported and medical care sought immediately.
Various diagnostic tests are available to measure, under carefully controlled conditions, the length of time it takes to produce certain components of the final fibrin clot. The activated partial thromboplastin time (APTT) is performed and will typically be prolonged while a prothrombin time (PT) will likely be normal. Factor assays, measurement methods performed by the clinical laboratory, can determine the percentage of factors VIII and IX present compared to normal percentages. This information helps to confirm a diagnosis of hemophilia and identifies the type and severity of hemophilia present.
Families with a history of hemophilia can also have tests done during a pregnancy to determine whether the fetus will have hemophilia. Chorionic villous sampling is a test that examines proteins for deficiencies or defects that are characteristic of hemophilia. The test can be performed at 10 to 14 weeks; test performance is associated with a 1 percent risk of miscarriage. Amniocentesis is a method of withdrawing amniotic fluid from the placenta to allow examination of fetal cell DNA shed into the amniotic fluid, helping to identify genetic mutations. Amniocentesis can be performed at 15 to 18 weeks gestation and is associated with a one in 200 risk of miscarriage.
The treatment of hemophilia involves replacing or supplementing the deficient coagulation factors. Various preparations of factors VIII and IX are available to replace missing factors as needed. Cryoprecipitate, for example, is a single- or multiple-donor human plasma preparation rich in coagulation factors; it is made available as a frozen concentrate. Fresh frozen plasma is a single-donor preparation of factor-rich plasma; it is used primarily for replacing factor XI in individuals with hemophilia C. Concentrated 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. These preparations are administered directly into the individual's veins (intravenous administration).
The frequency of treatment with coagulation factors depends on the severity of the individual's disease. Relatively mild disease will only require treatment in the event of injury, or to prepare for scheduled surgical or dental procedures. More severe disease will require regular treatment to avoid spontaneous bleeding.
Appropriate treatment of hemophilia can decrease suffering and be lifesaving in the presence of hemorrhage. Complications associated with treatment, however, can also be quite serious. About 20 percent of all individuals with hemophilia A begin to produce antibodies in their blood against the specific factor protein; the presence of antibodies may then rapidly destroy infused factor VIII. The presence of such antibodies may greatly hamper efforts to prevent or stop a major hemorrhage.
Individuals who receive coagulation factors prepared from pooled donor blood were once at risk for serious infections that could be passed through the infusion of human blood products, such as the hepatitis virus and HIV. Concern has also been raised about the possibility of hemophiliacs contracting a fatal slow virus infection of the brain (Creutzfeldt-Jakob disease) from blood products. However, more sensitive testing techniques have been developed and as of 2004 were employed by the companies producing pooled precipitates from human plasma. These improved methods of donor testing, as well as methods of inactivating viruses present in donated blood, have greatly lowered the risk of infection.
Molecular biological techniques have introduced gene therapies as new treatment possibilities for hemophilia. Gene therapy involves sophisticated methods of transferring new genes to hemophiliacs, correcting deficiencies or defects in the clotting mechanism. These methods are being researched in the early 2000s.
Variations in the type and severity of hemophilia makes it difficult to generalize a prognosis, however, for individuals with mild hemophilia, the prognosis is quite good. Those with more severe hemophilia can also live relatively normal lives with careful management and avoidance of injury. Many individuals achieve normal life expectancy. Without treatment of bleeding episodes, severe muscle and joint pain and eventually permanent damage can occur. Much depends upon the physical activity level of the individual and the possibility of accidental injuries or surgeries required for other conditions, which cannot be predicted.
Because of its genetic origins, hemophilia cannot be prevented in those born with the inherited defects or factor deficiencies. However, individuals who have a family history of hemophilia may benefit from genetic testing and counseling before deciding to have a baby.
The most important way for individuals with hemophilia to prevent complications of the disease is to avoid activities that may lead to injury. Those individuals who require dental work or any type of surgery may need to be pre-treated with an infusion of factor VIII to avoid hemorrhage. Hemophiliacs should also avoid medications or drugs that promote bleeding; aspirin is one such medication and many prescription drugs have anticoagulant properties.
When a child has an inherited coagulation disorder such as hemophilia, parents will be concerned about the possibility of trauma or injury that may lead to potentially dangerous bleeding episodes. The watchfulness of parents along with effective management of hemophilia by physicians can help the child to lead a relatively normal life. Careful avoidance of injury is essential. Counseling is available to help children handle the psychosocial aspects of living with hemophilia. Education is available from public health organizations to help parents be informed about their child's condition.
Amplification —A process by which something is made larger. In clotting, only a very few chemicals are released by the initial injury; they trigger a cascade of chemical reactions which produces increasingly larger quantities of different chemicals, resulting in an appropriately-sized, strong fibrin clot.
Coagulation factors —Specific coagulation proteins in the blood required for clotting. Coagulation proteins are designated with roman numerals I through XIII.
Fibrin —The last step in the blood coagulation process. Fibrin forms strands that add bulk to a forming blood clot to hold it in place and help "plug" an injured blood vessel wall.
Hemorrhage —Severe, massive bleeding that is difficult to control. The bleeding may be internal or external.
Mutation —A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease. This change can be transmitted to offspring.
Platelet —A cell-like particle in the blood that plays an important role in blood clotting. Platelets are activated when an injury causes a blood vessel to break. They change shape from round to spiny, "sticking" to the broken vessel wall and to each other to begin the clotting process. In addition to physically plugging breaks in blood vessel walls, platelets also release chemicals that promote clotting.
Trauma —Serious physical injury. Also refers to a disastrous or life-threatening event that can cause severe emotional distress, including dissociative symptoms and disorders.
See also Coagulation disorders.
Britton, Beverly. Diseases and Disorders: Hemophilia. Farmington Hills, MI: Gale, 2003.
Khoury, Muin J., Wylie Burke, and Elizabeth J. Thomson, eds. Genetics and Public Health in the 21st Century: Using Genetic Information to Improve Health and Prevent Disease. New York: Oxford University Press, 2000.
McDougald, Monroe. Hemophilia Care in the New Millennium. Lancaster, UK: Kluwar Academic Publishers, 2001.
Rodriguez-Merchan, E. C., et al. Inhibitors in Patients with Hemophilia. Oxford, UK: Blackwell Publishing, 2002.
National Hemophilia Foundation. 116 West 32nd St., 11th Floor, New York, NY 10001. Web site: <www.hemophilia.org>.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812–8923. Web site: <www.rarediseases.org>.
"Hemostatis and Coagulation." The Merck Manual Online, 2003. Available online at <www.merckcom/pubs/mmanual/section11/chapter131.131c.htm> (accessed October, 22, 2004).
March of Dimes. Available online at <www.modimes.org> (accessed October 22, 2004).
L. Lee Culvert Jennifer F. Wilson, MS
Culvert, L.; Wilson, Jennifer. "Hemophilia." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1G2-3447200270.html
Culvert, L.; Wilson, Jennifer. "Hemophilia." Gale Encyclopedia of Children's Health: Infancy through Adolescence. 2006. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3447200270.html
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 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.
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.
Khoury, Muin J., Wylie Burke, and Elizabeth J. Thomson, editors. Genetics and Public Health in the 21st Century: Using Genetic Information to Improve Health and Prevent Disease. New York: Oxford University Press, 2000.
Resnick, Susan. Blood Saga: Hemophilia, AIDS, and the Survival of a Community. Berkeley: University of California Press, 1999.
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://firstname.lastname@example.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〉.
Wilson, Jennifer. "Hemophilia." Gale Encyclopedia of Medicine, 3rd ed.. 2006. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1G2-3451600766.html
Wilson, Jennifer. "Hemophilia." Gale Encyclopedia of Medicine, 3rd ed.. 2006. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3451600766.html
Hemophilia A and hemophilia B are genetic disorders in the blood-clotting system, characterized by bleeding into joints and soft tissues, and by excessive bleeding into any site experiencing trauma or undergoing surgery. Hemophilia A and B are clinically indistinguishable. Both have the same type of bleeding manifestations, and both affect males almost exclusively. The two conditions can be distinguished by detecting the responsible defective proteins.
Contrary to popular belief, individuals with hemophilia rarely bleed excessively from minor cuts or scratches. Hemophilia A and B are both worldwide in distribution, affecting all racial and ethnic groups. The prevalence of hemophilia A is approximately 1 in 10,000 males, and that of hemophilia B is 1 in 30,000 males.
The disorder was recognized (although not named) in Babylonian times. A second-century Jewish rabbi gave permission for a woman not to have her third son circumcised after her first two sons died from the procedure. No doubt the most famous carrier of hemophilia was the nineteenth-century Queen Victoria, whose son, Prince Leopold, had the disorder, and whose two daughters inherited and passed on the gene. Ultimately several of the European royal families were affected by Queen Victoria's gene.
There are a number of clotting factors that interact to form a stable blood clot following injury or surgery. Each factor has a name and is produced in certain cells (usually in the liver), encoded by a certain gene. Hemophilia is caused by a defect in one of these genes. In the case of hemophilia A, factor VIII (FVIII) is deficient or absent. In hemophilia B, FIX is deficient in amount or absent, or it does not function properly.
The genes encoding FVIII and FIX are on the long arm of the X chromosome. Because males have only one X chromosome, hemophilia A and hemophilia B affect males almost exclusively. If a boy's X chromosome has the defective gene that causes hemophilia A or B, the boy will have hemophilia.
Since boys with hemophilia have only an X chromosome carrying the defective gene that causes hemophilia A or B, and no gene for the production of normal FVIII (or FIX), and since fathers pass an X chromosome on to their daughters, all of their daughters will be "obligate carriers" for hemophilia. Obligate carriers—individuals who are definitely carriers—include daughters of men with hemophilia and women who have a maternal family history of hemophilia and one or more affected sons or grandsons.
In general, such carrier females do not bleed excessively, as their other X chromosome, with a gene for normal FVIII (or FIX) production, results in intermediate levels of FVIII (or FIX). However, carrier females have a fifty-fifty chance of passing their X chromosome that bears the hemophilia gene to each child they might have. A son would have an equal chance of being normal or having hemophilia. A girl would have an equal chance of being normal or being a carrier, like her mother.
Gene Defects Causing Hemophilia
Hundreds of defects in the FVIII gene have been shown to cause hemophilia A. These include deletions of varying sizes in the gene, stop codons , frameshift mutations, and point mutations. Inversion of the gene is the most common mutation. The same types of defects are found in the FIX gene. This makes population screening for hemophilia impractical: There are too many possible mutations to screen for. However, affected members of a given family will all have the same defect.
It is useful to determine (by gene analysis) which defect is present in the FVIII or FIX gene of a particular family with hemophilia, so that one can look for this defect in possible carrier females. Identification of carrier females permits genetic counseling and decision making, on the part of parents, regarding childbearing.
Detection of FVIII or FIX Gene Defect in Family: Carrier Detection
A number of different techniques are available for carrier detection. Linkage analysis using DNA polymorphisms to track defective FVIII or FIX genes is possible in large families. Use of intragenic polymorphisms in both the FVIII and FIX genes allows precise detection of carrier females in most families studied. In persons with hemophilia A, the FVIII gene inversion can be tested for by Southern blotting .
If the gene defect in the family is not known, the inversion mutation in an affected male is generally sought first, as this mutation accounts for at least 20 percent of all cases of hemophilia A, and the test is relatively simple to perform. Although more time-consuming, point-mutation screening also can be done, using a variety of methods. For researchers working on the FVIII or FIX genes, there are sites on the Internet that are valuable resources, as they contain regularly updated listings of all reported mutations in each of these genes, and other useful information.
Because of a high mutation rate, approximately one-third of infants found to have hemophilia A or B have no family history of the disorder, the condition having occurred spontaneously. However, hemophilia is genetically transmitted to future generations.
Differences in Severity of Hemophilia
There are different degrees of severity of hemophilia A and B. Clinical severity usually correlates with the individual's circulating FVIII or FIX level (determined by doing an FVIII or FIX assay on a venous blood sample). The severity is generally the same in all affected members of a family.
Normal values for FVIII and FIX can range between 50 and 150 percent of the mean value, while severely affected individuals generally have levels of less than or equal to 1 percent, moderately affected persons 1 to 5 percent, and mildly affected persons 5 to 35 percent. Severely affected individuals often have spontaneous joint and muscle hemorrhages, whereas mildly affected persons bleed only with trauma or surgery.
Treatment for bleeding episodes consists of replacing the missing clotting factor by intravenous infusion of FVIII (or FIX). There are both human plasma-derived FVIII and FIX concentrates and recombinant DNA-derived FVIII and FIX concentrates. The useful life for both proteins (FVIII and FIX) once infused is relatively short (on average, half is degraded within twelve hours for FVIII and within eighteen hours for FIX). Thus for serious bleeding episodes or surgery, frequent repeat dosing (or continuous infusion) is often necessary.
Prophylaxis is also used, particularly in persons with severe hemophilia A or B. This consists of giving FVIII three times weekly, and FIX twice weekly (in view of its longer half-life, once infused). The aim of prophylaxis (which is often begun between age one and three) is to prevent joint bleeding (and the resulting increase in joint destruction and disability).
Persons with mild hemophilia A can often be treated with the synthetic agent DDAVP (1-deamino-8-D-arginine vasopressin). This analogue of the naturally occurring antidiuretic hormone vasopressin results in a rapid release of whatever FVIII (and another large plasma glycoprotein, von Willebrand factor) is in the individual's body storage sites. Thus, following intravenously administered DDAVP, FVIII (and von Willebrand factor) increase (two-to tenfold), but then fall back to baseline within approximately twelve to fifteen hours. This drug comes in several formulations, for intravenous , subcutaneous , and intranasal use.
It is hoped that gene therapy for persons with severe hemophilia may eventually become a realistic option. In early 2002 there were several ongoing phase-one trials (very early research studies) in human subjects with severe hemophilia, using different vectors and different techniques. However, formidable challenges remain.
see also Blotting; Disease, Genetics of; Genetic Counseling; Inheritance Patterns; Mutation; Transposable Genetic Elements; X Chromosome.
Jeanne M. Lusher
Lakich, Delis, et al. "Inversions Disrupting the Factor VIII Gene as a Common Cause of Severe Haemophilia A." Nature Genetics 5 (1993): 236-241.
Lillicrap, David. "The Molecular Basis of Haemophilia B." Haemophilia 4 (1998): 350-357.
Potts, D. M., and W. T. W. Potts. Queen Victoria's Gene: Haemophilia and the Royal Family. Gloucestershire, U.K.: Sutton Publishing, 1995.
Haemophilia B Mutation Database. King's College London. <http://www.kcl.ac.uk/ip/petergreen/haemBdatabase.html>.
Hemophilia: The Royal Disease. University at Buffalo, SUNY. <http://ublib.buffalo.edu/libraries/projects/cases/hemo.htm>.
National Hemophilia Foundation. <http://www.hemophilia.org>.
One form of hemophilia is due to the insertion of a transposable genetic element. (DNA sequence that can be copied and moved in the genome).
Lusher, Jeanne M.. "Hemophilia." Genetics. 2003. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1G2-3406500136.html
Lusher, Jeanne M.. "Hemophilia." Genetics. 2003. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3406500136.html
Haemophilus is a bacterial genus. The bacteria in this genus all share the characteristic of preferring to grow on solid laboratory media that contains blood cells. The blood supplies two factors that Haemophilus species require for growth. These are X factor and V factor. The utilization of these factors and of the blood cells causes the destruction of the cells and various characteristic reactions in the blood agar . Indeed, the name of the genus arise from these reactions.
Haemophilus are Gram negative in their Gram staining behavior and are very tiny rods in shape. The bacteria can display different shapes, and so is one of the types of bacteria known as pleomorphic bacteria. A hallmark of Haemophilus species is the formation of small colonies that are described as "satellites" around colonies of Staphylococcus.
In humans, Haemophilus is a normal resident of the throat and nose. However, spread of the bacteria beyond these sites can cause infections.
Haemophilus influenzae commonly infects children, causing a respiratory infection. This infection typically strikes those who already have the flu. The bacteria that cause these relatively severe reactions possess a glycocalyx that surrounds the each bacterium. The glycocalyx help thwart the host's immune response. Types of Haemophilus influenzae that cause less severe infections of the ears and the sinuses typically do not possess the glycocalyx.
Haemophilus influenzae infections can spread beyond the lungs. Spread to the central nervous system can result in an infection and inflammation of the sheath that surrounds nerve cells (meningitis ). Haemophilus influenzae type b (which is also known as Hib) is particularly noteworthy in regard to meningitis. Hib can cause of fatal brain infection in young children.
Hib infections were once more common and dangerous. Now, however, the availability of a vaccine and the widespread requirement for a series of vaccinations early in life has greatly reduced the incidence of Hib meningitis.
Haemophilus can also spread to the airway. In that location, an infection known as epiglottits can be produced. The resulting obstruction of the airway in children less than 5 years of age can be fatal.
Other species of note include Haemophilus aegyptius, the cause of conjunctivitis (or pinkeye), a very contagious disease in children, and Haemophilus ducreyi, a sexually transmitted disease that causes genital ulceration.
See also Bacteria and bacterial infection; Blood agar, hemolysis, and hemolytic reactions
"Haemophilus." World of Microbiology and Immunology. 2003. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1G2-3409800259.html
"Haemophilus." World of Microbiology and Immunology. 2003. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3409800259.html
hemophilia (hē´məfĬl´ēə,–fēl´yə), genetic disease in which the clotting ability of the blood is impaired and excessive bleeding results. The disease is transmitted through females but almost invariably affects male offspring only. A male born to a carrier mother has a 50% chance of having the disease. A hemophiliac cannot pass the disease to his sons, but all his daughters will be carriers. There are two diseases usually classified as hemophilia: hemophilia A (classical hemophilia, or Factor VIII deficiency) and hemophilia B (Christmas disease, or Factor IX deficiency).
Small wounds and punctures are usually not a problem for hemophiliacs and can be treated as in a nonhemophiliac. Uncontrolled internal bleeding, however, can result in pain and swelling and permanent damage, especially to joints and muscles. The symptoms often first appear in toddlers as their joints begin to bear weight.
Treatment and Screening
There is no cure for hemophilia, but treatment has been refined in recent years. In the 1960s, infusion of concentrated clotting factors replaced the whole-blood or plasma transfusions previously necessary, allowing most to administer preventive treatment at home. In the 1980s, however, many hemophiliacs became infected with hepatitis or HIV (the AIDS virus) that was present in contaminated concentrated clotting factor. Blood donors are now screened, and commercial products are now heat-treated to kill the viruses. Genetic testing can identify carriers of hemophilia, and the status of fetuses can be now be ascertained early in pregnancy. Treatments under study include gene therapy by insertion of healthy factor VIII or IX genes and fetal tissue implants.
Examples of the transmission of hemophilia have been found in several royal families. The family of Queen Victoria of England and, later, that of her granddaughter the Czarina Alexandra Feodorovna were affected. The apparent ability of Rasputin to check the hemophilia of the czarina's son was the basis of his hold over her and the czar. The family of Alfonso XIII of Spain, who married another granddaughter of Victoria, was also affected.
See S. Pemberton, The Bleeding Disease: Hemophilia and the Unintended Consequences of Medical Progress (2011).
"hemophilia." The Columbia Encyclopedia, 6th ed.. 2016. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1E1-hemophil.html
"hemophilia." The Columbia Encyclopedia, 6th ed.. 2016. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1E1-hemophil.html
Hemophilia (pronounced hee-muh-FIH-lee-uh) is a genetic disorder that often results in excessive bleeding. The condition can range from mild to severe. In its most serious forms, it can lead to death.
Injury to a blood vessel is a serious problem for the body. Blood may begin to leak out of the injured area. The body has developed a mechanism for protecting itself from this kind of damage. The mechanism involves the formation of a blood clot over the injured area to prevent loss of blood.
Blood clotting is a very complicated process. It involves blood cells known as platelets and at least twenty different chemical compounds. The first step in the clotting process is the formation of a temporary plug. The plug is formed of platelets that stick to the damaged area. The plug is soon covered by a more permanent structure consisting of fibrin (pronounced FI-brin). Fibrin is tissue that acts like a permanent patch or bandage on the injured area.
The production of fibrin takes place in a series of steps that requires thirteen different chemicals. These chemicals are known as "clotting factors." In order for fibrin to form, all thirteen clotting factors must be present in the blood.
Hemophiliacs (people who have hemophilia) may lack one or more clotting factors, or their bodies may not make enough of a clotting factor, or the clotting factor may not be made correctly. In any one of these cases, the patient's body is not able to make fibrin. An injury to a blood vessel cannot be properly repaired. Blood continues to escape from the damaged blood vessel.
Various types of hemophilia have been discovered. Each type results from problems with a particular clotting factor. Hemophilia A is the most common form of the disorder. It is caused by a defective clotting factor known as factor VIII. Hemophilia A can range from relatively mild to very severe. The severity of the disorder depends on how much factor VIII the patient's body is able to make.
Individuals with more than 5 percent of normal factor VIII have mild hemophilia. They are likely to experience bleeding problems only when having surgery or dental procedures. Individuals with 1 to 5 percent of normal factor VIII have moderate hemophilia. They may experience bleeding problems if they have a minor injury, such as a fall. Individuals with less than 1 percent of normal factor VIII have severe hemophilia. They may begin bleeding for no reason at all. Surgery and dental procedures can be very dangerous. About half of all hemophiliacs have this form of the disorder.
Hemophilia B is caused by a defective clotting factor known as factor IX. This type of hemophilia is also known as Christmas disease. The range of symptoms of hemophilia B is similar to that of hemophilia A.
Hemophilia C is very rare and is much more mild that hemophilia A or B. It is caused by a defective clotting factor known as factor XI.
Hemophilia: Words to Know
- A structure located inside the nucleus (center) of a cell that carries genetic information.
- Clotting factor:
- One of the chemicals necessary for blood clotting.
- A thick material formed over an injured section of blood vessel by the process of blood clotting.
- A chemical unit found in all cells that carries information telling cells what functions they are to perform.
- Severe, massive bleeding.
- A type of blood cell involved in the clotting of blood.
Hemophilia is a genetic disorder. A genetic disorder is a medical condition in which a person has one or more abnormal genes. Genes are the chemical units that are present in all cells. They tell cells what functions to perform. For example, everyone has certain genes that tell cells how to make clotting factors. There is one gene for making clotting factor I, one gene for clotting factor II, one gene for clotting factor III, and so on.
Sometimes a person inherits a defective gene from a parent. That defective gene carries no instructions, or the wrong instructions, for performing some function. A cell does not know how to make a certain material, such as clotting factor VIII, or it makes the material incorrectly. In such cases, a genetic disorder may develop.
Genes are arranged in cells on long strings known as chromosomes. Under a microscope, chromosomes look like a string of beads, in which genes are the individual beads.
All normal human cells contain twenty-three pairs of chromosomes. Half of the chromosomes come from the father, and half from the mother. One pair of chromosomes is the sex chromosomes. These two chromosomes determine sexual characteristics, along with other characteristics. Two types of sex chromosomes exist: an X chromosome and a Y chromosome. Men have one X and one Y chromosome. Women have two X chromosomes.
The genes for making clotting factors are located on X chromosomes. This means that males are more likely to have hemophilia than females. A female always has two X chromosomes. She may inherit one defective X chromosome, but she will probably not inherit two defective X chromosomes. Her normal X chromosome will still carry the correct instructions for making clotting factors.
Males, however, carry only one X chromosome. If the X chromosome a male inherits is defective, he will not have a normal X chromosome to compensate for the defective one. His cells will not receive the correct instructions for making clotting factors.
For this reason, hemophilia is almost entirely a disorder in males. The condition very rarely occurs among women. Even if women carry one defective X chromosome, they will not have the disorder. However, they will have the ability to pass the disorder on to their children. For that reason, a female with just one defective X chromosome is said to be a carrier for the disorder.
Spontaneous Gene Mutation
About 30 percent of all people with hemophilia A or B are the first members of their family to ever have the disease. These individuals have the unfortunate occurrence of a spontaneous mutation. In their early development some random genetic accident caused a defect in their X chromosome. Once
a genetic mutation takes place, offspring of the affected person can inherit the newly-created, flawed chromosome.
The primary symptom of hemophilia is bleeding. The amount of bleeding that occurs depends on how serious the patient's condition is. In the most severe cases, bleeding can cause serious health problems, including death.
Severe hemophilia is usually discovered before a child has reached the age of eighteen months. For example, circumcision can result in heavy bleeding. Toddlers with severe hemophilia are at serious risk because they fall frequently. Bleeding may occur in the soft tissue of the arms and legs. This bleeding may cause bruising and noticable lumps, but usually does not require treatment.
As a child becomes more active, bleeding into the muscles may occur. This form of bleeding is more serious and more painful. Muscle bleeds cause pressure on nerves. This pressure can cause pain, numbness, and damage to nerves.
Some of the most serious damage caused by bleeding occurs in joints, especially the knees and elbows. Repeated bleeding can cause scarring of the joints. Joints may become deformed and permanently damaged.
Bleeding in the head can be especially serious. Many people receive blows to the head, but they seldom suffer serious damage. In the case of hemophilia, a blow to the head can cause extensive bleeding in the brain. Since the skull cannot expand, the bleeding causes pressure on delicate brain tissue. Permanent brain damage may occur.
More serious accidents can cause even more extensive bleeding. A hemophiliac who is in a motor vehicle accident, for example, may suffer from massive hemorrhaging (bleeding) that can result in death.
Abnormal bleeding patterns are usually the first clue that a person has hemophilia. Simple bumps and bruises that result in uncontrolled bleeding are a common early symptom of hemophilia.
Diagnosis of hemophilia is confirmed with blood tests. These tests are able to measure how much of various clotting factors are present in the blood and how quickly they work to produce clots. These tests can be used to diagnose the type of hemophilia a person has and the seriousness of the condition.
Hemophilia can be treated with injections of missing clotting factors. Patients with hemophilia A receive injections of factor VIII, and those with hemophilia B get factor IX.
The frequency of treatment depends on the severity of the disease. People with mild hemophilia may require treatment only when they have been injured. They may also need treatment before surgery or dental work. Patients with more severe forms of the disorder may require regular injections of the missing factor.
THE ROYAL DISEASE
In 1837, Queen Victoria ascended to the throne of England. Although she was a much-loved ruler, she left a terrible legacy to her country. She was a carrier for the gene for hemophilia. Although she did not suffer from the disease herself, she passed it on to one of her sons. In addition two of her daughters and three of her granddaughters were also carriers of the gene for hemophilia. Five of Victoria's great-grandsons had the disease.
Queen Victoria's son Leopold, according to the Queen's own accounts, had "been four or five times at death's door" because of the disease. At the age of thirty-one, he fell and hit his head. Doctors could not stop the bleeding, and he died a few days later.
Victoria's descendents eventually passed the genes for hemophilia on to the Spanish and Russian Royal houses. Victoria's daughters Beatrice and Alice both married German princes. They transmitted the gene for hemophilia to their own daughters who married into the Spanish and Russian royal families. It is said that two of Victoria's great-grandsons who grew up in Spain played in a park where all the trees were wrapped with cloth to prevent their being injured.
One of Alice's daughters, Alix, married Nicholas II, son of Alexander III, Czar of Russia. Alix's son, Alexis, also inherited the gene for hemophilia. At the age of three, he was injured and nearly bled to death. Alexis' painful and difficult childhood was a great source of distress to Alix. She was comforted when a man named Grigory Rasputin was able to stop the boy's bleeding. Rasputin was honored by Nicholas and Alix. Rasputin's closeness to the royal family and rumored influence was a contributing factor in the decline of the czarist Russian empire.
The use of injections to treat hemophilia is accompanied by some possible complications. For example, in some cases, the body's immune system begins to make antibodies against factors contained in the injections. Antibodies are chemicals produced by the immune system to protect the body against infection. The immune system may become confused and react as if the injected factors are bacteria, viruses, or other harmful materials.
Complications may result from the way clotting factors are obtained for injections. In some cases, the clotting factors are obtained from people who have donated blood. The donated blood is usually prepared very carefully in order to obtain pure clotting factors. But sometimes mistakes happen. Harmful substances in donated blood may become part of the preparation given to hemophiliacs.
The worst example of this situation involved blood contaminated with the human immunodeficiency virus (HIV). HIV is the virus that causes AIDS (see AIDS entry). In the early years of the HIV epidemic, people who worked with blood did not know about the virus. They were not aware that blood donated by people with HIV also contained the virus. When that blood was used to produce clotting factors, the virus was part of the preparation given to hemophiliacs. Many hemophiliacs developed AIDS in this way. As of 1999, AIDS was still the leading cause of death among hemophiliacs because of this tragedy. Precautions have been put in place to ensure that contaminated blood is not used. The chance of HIV or other harmful agents being present along with clotting factors is very small.
The future of people with hemophilia is very hard to predict. For one thing, the severity of the condition varies widely, from very mild to very severe. Also, hemophiliacs differ in their degree of activity. The more active a hemophiliac is, the more likely injury is to occur.
There is only one way to prevent hemophilia. Parents who carry a defective X chromosome may pass that chromosome on to their children. If a male child inherits a defective X chromosome he will develop hemophilia. Adults can be tested to tell if they carry a defective X chromosome. They can use that information to make decisions about having children.
People who already have hemophilia can make decisions as to how best to prevent the worst conditions of their disorder. For example, they can avoid the most strenuous forms of work and exercise that might result in injury and bleeding. They also need to make special preparations when surgery or dental procedures are necessary.
FOR MORE INFORMATION
National Hemophilia Foundation. 116 West 32nd Street, 11th Floor, New York, NY 10001. (800) 42–HANDI.
"Hemophilia." UXL Complete Health Resource. 2001. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1G2-3437000157.html
"Hemophilia." UXL Complete Health Resource. 2001. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3437000157.html
—haemophiliac n. —haemophilic adj.
"haemophilia." A Dictionary of Nursing. 2008. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1O62-haemophilia.html
"haemophilia." A Dictionary of Nursing. 2008. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1O62-haemophilia.html
he·mo·phil·i·a / ˌhēməˈfilēə/ (Brit. hae·mo·phil·i·a) • n. a medical condition in which the ability of the blood to clot is severely reduced, causing the sufferer to bleed severely from even a slight injury. The condition is typically caused by a hereditary lack of a coagulation factor, most often factor VIII. DERIVATIVES: he·mo·phil·i·ac / -ˈfilēˌak/ n. he·mo·phil·ic / -ˈfilik/ adj.
"hemophilia." The Oxford Pocket Dictionary of Current English. 2009. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1O999-hemophilia.html
"hemophilia." The Oxford Pocket Dictionary of Current English. 2009. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1O999-hemophilia.html
"haemophilia." A Dictionary of Biology. 2004. Encyclopedia.com. (June 30, 2016). http://www.encyclopedia.com/doc/1O6-haemophilia.html
"haemophilia." A Dictionary of Biology. 2004. Retrieved June 30, 2016 from Encyclopedia.com: http://www.encyclopedia.com/doc/1O6-haemophilia.html
Hemophilia (he-mo-FIL-e-a) is a hereditary disorder in which the blood does not clot normally and excessive bleeding results.
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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.
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
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.
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.
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.
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.
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.
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
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 Victorias 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 II (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.
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.
tightness, pain, skin temperature change, and tingling or numbness. Early treatment is needed to prevent paralysis or permanent immobility.
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.
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.
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.
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.
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.
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.
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.
National Hemophilia Foundation http://www.infonhf.org/
World Foundation of Hemophilia http://www.wfh.org/
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