Hemophilia A

A deficiency of clotting Factor VIII (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.
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

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.

Inheritance Pattern – Women and Hemophilia. Hemophilia A is caused by an inherited sex-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.

Hemophilia Treatment

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.

Hemophilia-related HIV/AIDS

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.

von Willebrand Disease (vWD)

Like hemophilia, von Willebrand disease 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.

vWD Diagnosis and Treatment
Because the symptoms can be mild, vWD can be difficult to diagnose and often goes undetected. Your child’s doctor will take a family medical history to determine if other relatives have a bleeding disorder.

  • The tests to diagnose vWD may include:bleeding time factor VIII level test (also called factor VIII coagulant) – which measures the level of factor VIII and its ability to function.
  • von Willebrand factor antigen test (also called factor VIII antigen) – which measures the amount of von Willebrand factor. The disorder is considered mild if a person has 20% to 40% of the normal amount. It is severe if the amount is less than 10% of normal.
  • Ristocetin Cofactor activity test (also called factor VIII ristocetin cofactor) – which measures how well the von Willebrand factor is working
  • von Willebrand factor multimers test – which helps classify the type of vWD
  • Platelet function tests – which determine how well the platelets work and help identify the type of vWD or the presence of another disorder

Tests may need to be done more than once because these levels may rise and fall over time in an individual.

Women with Bleeding Disorders

Women of all ages who are symptomatic carriers of hemophilia, have von Willebrand disease, or other bleeding disorders, have special issues with bleeding because of obstetric and gynecological issues.Prolonged menstrual bleeding and prolonged bleeding after childbirth or miscarriage can be a problem. Long, heavy menstrual flows often lead to low iron levels. Therefore, women with bleeding disorders should routinely be tested for anemia. During pregnancy, levels of factors VIII and IX and von Willebrand factor usually increase in women with bleeding disorders. A woman with a bleeding disorder who becomes pregnant should see an obstetrician as soon as possible. This will ensure that the doctor can work with the local Hemophilia Treatment Center to provide prenatal and postnatal care for the woman and her unborn baby. Miscarriages and abortions, even early in the course of a pregnancy, can result in prolonged bleeding for women with bleeding disorders. Women with bleeding disorders who know or think they are miscarrying, or who are choosing to end a pregnancy, should promptly seek medical care as soon as possible.