What Is It?
Hemophilia is an inherited blood disease in which the blood lacks one or more of the clotting factors. Because of this lack, the blood is unable to form a clot, and even a small cut can result in prolonged bleeding and death. Even a bruise can cause severe pain because the blood that escapes from broken capillaries can leak into the joints and other body spaces, putting pressure on the nerve endings in those locations. Commonly called "bleeder's disease," or the "royal disease" because it was passed down through many of the royal families of Europe, hemophilia principally affects males. When hemophiliacs (people afflicted with hemophilia) suffer a trauma and begin to bleed, they are given a transfusion of fresh plasma or an injection of the clotting factor they lack. They can also be given clotting factors on a regular basis to prevent episodes of spontaneous bleeding. Suffering an occasional cut, scratch, or bruise is a normal consequence of life. When there is damage to the skin and a blood vessel ruptures, bleeding occurs. The human body is then able to initiate a series of reactions that cause the bleeding to stop. First, platelet cells in the blood move toward and attach to the site of the wound. The platelets are further held in place by strands of fibrin. The formation of the strands is the key event in a complex series of enzymatic reactions that are still somewhat of a mystery today. Without this cascade clotting process, people would be in danger of bleeding to death from very minor injuries. As of 2007, there are about 18,000 people in the United States with hemophilia and 400 babies born each year with the disorder.
Description:
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. 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 (Gale 2007). Hemophiliacs 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 a 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 (2007). 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.
Symptoms:
In the case of severe hemophilia, the first bleeding event usually occurs prior to 18 months of age. In fact, toddlers are at particular risk, because they fall so frequently. 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 permanent deformities. 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 (The Gale Encyclopedia of Science 2011). Other symptoms may include extensive bleeding in the:
Description:
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. 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 (Gale 2007). Hemophiliacs 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 a 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 (2007). 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.
Symptoms:
In the case of severe hemophilia, the first bleeding event usually occurs prior to 18 months of age. In fact, toddlers are at particular risk, because they fall so frequently. 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 permanent deformities. 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 (The Gale Encyclopedia of Science 2011). Other symptoms may include extensive bleeding in the:
- Soft tissue (arms and legs)
- Muscles (pressure on nerves)
- Joints (knees and elbows)
- Head (brain and brain tissue)
(Hemophilia – Causes, Symptoms, Diagnosis And Treatment 2011)
What Causes It?
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. Changes in the F8 gene are responsible for hemophilia A, while mutations in the F9 gene cause hemophilia B. The F8 gene provides instructions for making a protein called coagulation factor VIII. A related protein, coagulation factor IX, is produced from the F9 gene. Coagulation factors are proteins that work together in the blood clotting process. Mutations in the F8 or F9 gene lead to the production of an abnormal version of coagulation factor VIII or coagulation factor IX, or reduce the amount of one of these proteins. The altered or missing protein cannot participate effectively in the blood clotting process. As a result, blood clots cannot form properly in response to injury.
Inherited Hemophilia:
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 (2007). 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:
As for the spontaneous gene mutation possibility, 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.
Inherited Hemophilia:
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 (2007). 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:
As for the spontaneous gene mutation possibility, 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.
Hemophilia A and B are both caused by a genetic defect present on the X chromosome. Approximately 70 percent of people with hemophilia A or B inherit the disease. The remaining 30 percent develop the disease due to a spontaneous genetic mutation (Gale 2010).
How Do We Fix It?
Various types of factors VIII, for hemophilia A, and IX, for hemophilia B, 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 of treatment can also be quite serious. About 20 percent of all patients with hemophilia A begin to produce chemicals within their bodies that rapidly destroy infused factor VIII. The presence of such a chemical may greatly hamper efforts to prevent or stop a major hemorrhage (2011). 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, is frequently contracted from pooled factor preparations. Most frighteningly, pooled factor preparations in the early 1980's were almost all contaminated with human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS). Currently, careful methods of donor testing, as well as methods of inactivating viruses present in donated blood, have greatly lowered this risk, but not before huge numbers of hemophiliacs were infected with HIV. In fact, some statistics show that, even today, the leading cause of death among hemophiliacs is AIDS.
Theoretical Cure:
In the early 1980's, a new method of manufacturing the required blood factors came into wider use. By genetic engineering, the normal human gene can be cloned into cell lines, a cell culture selected for uniformity from a cell population derived from a usual homogeneous tissue source, that can produce large amounts of, for example, human factor VIII. This approach eliminates the potential problems from contaminated human blood supplies. Another approach, which may well be adopted in the future, is gene therapy, which would directly replace the faulty gene in the patient, which would either be the F8 or F9 gene depending on which type of the disease you have (World of Genetics 2007). In addition to eliminating many of the side effects associated with previous therapies, proponents of gene therapy say that it will provide a lifelong cure for a patient if performed at the somatic level, while germ line gene therapy could even eliminate this disorder from the human species. Along with these, another theoretical cure might be to take the lacking clotting factor and "insert" it into stem cells within the body. With the lacking clotting factor placed inside, the stem cells can do their job which is to replenish cells of that type when old cells die, which would then create more of the missing clotting factor.
Theoretical Cure:
In the early 1980's, a new method of manufacturing the required blood factors came into wider use. By genetic engineering, the normal human gene can be cloned into cell lines, a cell culture selected for uniformity from a cell population derived from a usual homogeneous tissue source, that can produce large amounts of, for example, human factor VIII. This approach eliminates the potential problems from contaminated human blood supplies. Another approach, which may well be adopted in the future, is gene therapy, which would directly replace the faulty gene in the patient, which would either be the F8 or F9 gene depending on which type of the disease you have (World of Genetics 2007). In addition to eliminating many of the side effects associated with previous therapies, proponents of gene therapy say that it will provide a lifelong cure for a patient if performed at the somatic level, while germ line gene therapy could even eliminate this disorder from the human species. Along with these, another theoretical cure might be to take the lacking clotting factor and "insert" it into stem cells within the body. With the lacking clotting factor placed inside, the stem cells can do their job which is to replenish cells of that type when old cells die, which would then create more of the missing clotting factor.