A deficiency of clotting Factor VIII (factor 8) is classified as Hemophilia A. It is a hereditary disorder in which the clotting ability of the blood is impaired and excessive bleeding results. Uncontrolled internal bleeding can result in pain, swelling, and permanent damage, especially to joints and muscles.
Hemophilia A is caused by an inherited gender-linked recessive trait with the defective gene located on the X chromosome. Females are carriers of this trait. Fifty percent of the male offspring of female carriers have the disease and 50% of their female offspring are carriers. All female children of a male with hemophilia are carriers of the trait, and are called obligate carriers. One third of all cases of hemophilia A occur when there is no family history of the disorder. Called a spontaneous mutation, these cases of hemophilia develop as the result of a new or spontaneous gene mutation. Genetic counseling may be advised for carriers. Female carriers can be identified by a testing procedure called DNA Carrier Testing. The only way a female could have hemophilia is if her father has it and her mother carries the gene, or if she developed Aquired Hemophilia which is very rare. Women who are carriers can also be asymptomatic carriers, whereby they do experience factor deficiencies.
Severity of symptoms can vary, and severe forms usually become apparent early in life. Prolonged bleeding is the hallmark of hemophilia A and typically occurs when an infant is circumcised as hemophilia occurs primarily in boys. Additional bleeding manifestations make their appearance when the infant becomes mobile.
Mild cases may go unnoticed until later in life when there is excessive bleeding and clotting problems in response to dental procedures, surgery or trauma.
Generally, the first bleeding episode occurs before 18 months of age, often after a minor injury. A child who has hemophilia bruises easily. Even an injection into a muscle can cause bleeding that results in a large bruise (hematoma). Recurring bleeding into the joints and muscles can ultimately lead to crippling deformities.
Internal bleeding may occur anywhere in the body. Bleeding into joints, however, is most common. The incidence of hemophilia A is 1 out of 10,000 live male births. About 17,000 Americans have hemophilia. Women may have it, but it’s very rare. There is no cure for hemophilia. With proper treatment and specialized management, the outcome is good. Most men with hemophilia are able to lead successful and relatively normal lives.
Bleeding episodes can also be life threatening when it occurs in sensitive areas. Bleeding can swell the base of the tongue until it blocks the airway, making breathing difficult. A slight bump on the head can trigger substantial bleeding in the skull, causing brain damage and death. A doctor may suspect hemophilia in a child whose bleeding is unusual. A laboratory analysis of blood samples can determine whether the child’s clotting is abnormally slow. If it is, the doctor can confirm the diagnosis of hemophilia A and can determine the severity by testing the activity of factor VIII.
Hemophilia B (also called “Christmas disease”) is a deficiency in clotting factor IX. Hemophilia A is 7 times more common than Hemophilia B. The incidence of Hemophilia B is 1 out of 34,500 men. The outcome is good with proper treatment and specialized management. Most people with Hemophilia B are able to lead successful and relatively normal lives. (see Hemophilia A information above to learn about how hemophilia affects)
Both Hemophilia A and B are treated by infusing a factor product that replaces the patient’s missing clotting factor. The amount infused depends upon the severity of the bleeding episode, the site of the bleed, and the weight of the patient. Factor products are intended for home use and can be self-administered (self-infused), either on a regular basis to prevent bleeding or at the first sign of bleeding. Prophylaxis is the treatment method most commonly used. It involves infusing factor product on a regular schedule in order to prevent bleeding episodes from occurring. By treating before a bleed occurs, factor levels in the blood are more normalized which helps to prevent bleeding episodes and the pain and damage they cause. Both the dose and frequency of factor replacement depend on the severity of the bleeding problem. The dose is adjusted according to the results of periodic blood tests. During a bleeding episode, higher doses of factor product are often needed.
To prevent a bleeding crisis, people with hemophilia and their families can learn to administer factor products at home, and in advance of a heavy period of physical activity, or at the first signs of bleeding.
Centers of excellence for the treatment of bleeding disorders exist throughout the country. Arizona is fortunate to have two centers, one in Phoenix, and one in Tucson. The Centers for Disease Control have established that people who do not seek treatment from a Hemophilia Treatment Center (HTC), have an 80% greater chance of morbidity and mortality than those patients who do. It is recommended that each hemophilia patient receive an annual checkup, called an annual comprehensive evaluation. At this visit, patient’s are seen by a hematologist who specializes in bleeding disorder care, a physical therapist, a hemophilia nurse, a social worker, and others who are integral to bleeding disorder care in a one-stop visit. By bringing together multiple disciplines in one visit, patients are evaluated on many levels. The medical staff then meet to make treatment recommendations in a coordinated effort to enhance the patient’s treatment and quality of life.
Like hemophilia, von Willebrand Disease (VWD) is a hereditary deficiency or abnormality of clotting factor in the blood. In this case, it is the von Willebrand factor which is a protein that affects platelet function. It’s the most common hereditary disorder of platelet function, affecting both women and men. The disease is estimated to occur in 1% to 2% of the population. The disease was first described by Erik von Willebrand, a Finnish physician, who reported a new type of bleeding disorder among island people in Sweden and Finland. In von Willebrand disease, blood platelets don’t stick to holes in blood vessel walls. Platelets are tiny particles in the blood that clump together at the site of an injury to prepare for the formation of a blood clot. von Willebrand factor causes them to bind to areas of a blood vessel that are damaged. If there is too little von Willebrand factor, or the factor is defective, platelets do not gather properly when a blood vessel is injured. von Willebrand factor is found in plasma, platelets, and blood vessel walls. When the factor is missing or defective, the first step in plugging a blood vessel injury (platelets adhere to the vessel wall at the site of the injury) doesn’t take place. As a result, bleeding doesn’t stop as quickly as it should, although it usually stops eventually. There are no racial or ethnic associations with the disorder. A family history of a bleeding disorder is the primary risk factor.
Researchers have identified many variations of the disease, but most fall into the following classifications:
Type I: Most common and mildest form of von Willebrand disease. Levels of von Willebrand factor are lower than normal. Levels of factor VIII may also be reduced.
Type II: In these people, the von Willebrand factor itself has an abnormality. Depending on the abnormality, they may be classified as having Type IIa or Type IIb. In Type IIa, the level of von Willebrand factor is reduced as is the ability of platelets to clump together. In Type IIb, although the factor itself is defective, the ability of platelets to clump together is actually increased.
Type III: Severe von Willebrand disease. These people may have a total absence of von Willebrand factor and factor VIII levels are often less than 10%.Pseudo (or platelet-type) von Willebrand disease: This disorder resembles Type IIb von Willebrand disease, but the defects appears to be in the platelets, rather than the von Willebrand factor.
Once in a while, people develop what appears to be von Willebrand disease later in life. When this occurs in those who have no family history of the disease, it is thought that they’re probably producing antibodies that destroy or decrease the amount of von Willebrand factor. Some other people have “acquired” a form of the disease in association with another disorder, such as rheumatoid arthritis, systemic lupus erythematosus, kidney disease and certain cancers.
The life span of patients is usually normal length. Since the disease is genetically transmitted, genetic counseling may be recommended for parents. von Willebrand disease can be more complicated for women because of obstetric and gynecological issues.
Inheritance Pattern (VWD)
Like hemophilia, the disease is passed down through the genes. But unlike hemophilia, which usually affects only males, von Willebrand disease occurs in males and females equally. A man or woman with the disease has a 50% chance of passing the gene on to his or her child. Types I and II are usually inherited in what is known as a “dominant” pattern. This means that if even one parent has the gene and passes it onto a child, the child gets the disease. Whether the child has no symptoms, mild symptoms, or, less commonly, severe symptoms, he or she definitely has the disease. Regardless of severity of the symptoms, the child can still pass the gene on to his or her own offspring. Type III von Willebrand disease, however, is usually inherited in a “recessive” pattern. This type occurs when the child inherits the gene from both parents. Even if both parents have mild or asymptomatic disease, their children are likely to be severely affected. These patterns of inheritance differ from hemophilia, which is caused by a defect in one of the “sex linked” chromosomes. A man with hemophilia cannot pass the gene on to a son, because the abnormality is carried on the X chromosome, and a man contributes only a Y chromosome to his male offspring. von Willebrand disease is found on the autosomal chromosomes and therefore can be inherited by either males or females. von Willebrand disease can often be traced through several generations in a family. Some have symptoms while others just carry the gene.
Research and Studies
During the late 1970′s and early 1980′s, factor products were manufactured using donations of human blood. These donations contained the HIV virus which causes AIDS. As a result, approximately 60% of hemophiliacs who were treated contracted the HIV virus.
The death of thousands of people with hemophilia drove the medical and scientific community to find to create safe factor products. Today, only a few products contain elements of donated blood but these products include safety steps in the manufacturing process such as heat treatment and filtration to guard against any virus ending up in the finished product. The good news is that most of the products are now manufactured synthetically.
Though these products are safer to use than they have ever been before, people who infuse any medication into their veins take a certain risk. There have been product recalls due to manufacturing errors, improper temperatures during shipping, and cracked vials. There have also been recalls of the devices used in the infusion process (needles, tubing, syringes) for improper manufacturing techniques or unsterile packaging.
Hepatitis is an inflammation of the liver that occurs when the liver is injured or infected. It can range from being asymptomatic to becoming a life-threatening condition. Symptoms may include fatigue, nausea, vomiting, muscle and joint aches, liver tenderness and enlargement and/or weight loss. Hepatitis can be acute (lasting less than six months) or chronic. It occurs commonly throughout the world.
Hepatitis can be caused by any substance that damages the liver, including alcohol, drugs, chemicals, viruses or a combination of any of these. Hepatitis caused by viruses is called viral hepatitis and can be transmitted through blood and blood products.
Six different viruses are now known to cause hepatitis—hepatitis A, B, C, D, E and G. Hepatitis A, B and C account for almost 95% of all cases of viral hepatitis. The other strains are uncommon.
Today’s factor products are much safer than those of the past, though there is still some risk of getting hepatitis from clotting factor. Screening methods to identify donors with hepatitis have become more sensitive, greatly lowering the chances of transmitting one of the hepatitis viruses. Also, new viral inactivation methods now are being used on clotting factor products that make them much safer to use. As of 1997, there have been no reports of hepatitis C transmission through clotting factor that has been treated with these new processes. Hepatitis B and D are also killed by these methods. There is no known case of hepatitis E transmission through blood products. Small numbers of people with hemophilia have been exposed to hepatitis G, probably through blood products. Hepatitis A has been found in solvent detergent-treated clotting factor, in part because hepatitis A can resist the viral-killing methods now being used. Transmission of hepatitis A remains a risk for people with bleeding disorders who use plasma-derived products. However, hepatitis A may be prevented by immunization with a vaccine.
Today’s blood safety measures, though highly advanced, are not perfect. Whole blood and blood components, including packed red blood cells, platelets and cryoprecipitate cannot be treated with currently available virus-killing methods. Plasma may now be created with the same virus-killing methods (solvent-detergent plasma) used for hemophilia products. This is because these methods would damage or inactivate important blood components, making these blood products useless. According to recent figures, for each unit of blood the risk of getting hepatitis C is less than one in 103,000, while the risk of getting hepatitis B is one in 63,000. As a health precaution, it is advised that persons with bleeding disorders get vaccines against both hepatitis A and hepatitis B. They should also be tested for hepatitis C on a yearly basis. There is, however, no vaccine for hepatitis C.
High-risk activity that may lead to the transmission of hepatitis includes direct sexual contact with an infected person, sharing needles and coming into contact with infected blood. In some cases of hepatitis, little is known about how the infection is acquired.
Good hygiene helps prevent the spread of hepatitis A. Because the stool of people with hepatitis A is infectious, stool samples must be handled with special care. The same is true for the blood of people with any type of acute hepatitis. On the other hand, infected people don’t require isolation—it does little to prevent the transmission of hepatitis A, and it won’t prevent the transmission of hepatitis B or C.
Vaccinations are available against hepatitis A and B. Vaccination is especially important for people at risk for contracting hepatitis B, though it isn’t effective once the disease is established. For these various reasons, universal vaccination of all people against hepatitis B is being increasingly recommended.
A hepatitis B vaccine is recommended for all children by the American Academy of Pediatrics. A hepatitis A vaccine is recommended for all individuals two years of age and older with hemophilia and other congenital bleeding disorders.
Hepatitis A vaccines are given to people who are at a high risk of acquiring the infection, such as travelers to parts of the world where the disease is widespread. No vaccines are available against the hepatitis C, D and E viruses.
People who haven’t been vaccinated and are exposed to hepatitis may receive an antibody preparation (immune serum globulin) for protection.
The infection can be detected by simple, routine blood tests performed by doctors who suspect infection. Unfortunately, many people with hepatitis are never tested because they have no symptoms; by the time their infection is discovered, serious liver damage may have occurred. If someone thinks he or she may be infected, a doctor should be seen as soon as possible.
People with unusually severe acute hepatitis may require hospitalization, but in most cases treatment isn’t necessary. After the first several days, a person’s appetite usually returns and they don’t need to stay in bed. Severe restriction of diet or activity are unnecessary, and vitamin supplements are not required. Most people can safely return to work after the jaundice clears, even if their liver function test results aren’t quite normal.
Acute viral hepatitis symptoms can range from minor flu-like illness to liver failure. Hepatitis B is usually more serious than hepatitis A and is occasionally fatal, especially in elderly people. The course of hepatitis C is unpredictable. The acute illness is usually mild, but liver function may improve, stay the same or worsen over months to years. Fifteen percent of persons will spontaneously clear the virus and only 15% will develop severe liver failure.
A person with acute viral hepatitis usually recovers after four to eight weeks, even without treatment.
- Hepatitis A rarely if ever becomes chronic.
- Hepatitis B becomes chronic in 5 to 10 percent of the infected people and can be mild or full-blown.
- Hepatitis C has the greatest likelihood of becoming chronic—about a 70% chance. About one-third of chronic carriers have normal liver enzymes, and 70% will persist with elevated liver enzymes.
Though usually mild and often without symptoms, hepatitis C is a serious problem because about 20% of the infected people may eventually develop cirrhosis of the liver.
A person with acute viral hepatitis can become a chronic carrier of the virus. In the carrier state, the person has no symptoms but is still infected. This situation occurs only with hepatitis B and C, not hepatitis A. A chronic carrier has a higher chance (about six times the risk) of developing liver cancer.