Bleeding Disorders FAQs
What is hemophilia?
Hemophilia is a sex-linked, hereditary blood clotting disorder that results in excessive bleeding. The bleeding can occur spontaneously and/or after injury. Bleeding episodes may be external or internal into joints, muscles, the abdominal cavity, the brain, and other organs. The bleeding episodes are painful, and, unless treated promptly, can lead to crippling deformities of the joints or life threatening bleeds in the body cavity or head.
Who is affected by hemophilia?
According to the Centers for Disease Control and Prevention (CDC), Hemophilia affects approximately 19,000 people in the United States. About 400 babies are born each year with the disorder. Severe hemophilia occurs almost exclusively in males.. Women who are carriers of the gene may manifest milder forms of hemophilia. .Hemophilia affects all racial, national, and socioeconomic groups. It is a hereditary disorder, which means that it is passed from parent to child at birth. However, in about one third of the cases there is no family history of the disorder.
What causes hemophilia?
Hemophilia is caused by a change in the FVIII ( factor 8 ) or FIX ( factor 9 ) gene located on the X chromosome. This gene contains the code for the FVIII or FIX protein, necessary for normal blood clotting.
In normal blood clotting, a complex interaction of at least 14 plasma proteins (or factors) results in a gelatinous, fibrillar plug that seals leaks in damaged blood vessels. One of these proteins is lacking or deficient in people with hemophilia. Because of this the blood does not form a firm clot. People with hemophilia will not bleed excessively from a superficial cut or injury. Patients generally bleed longer not faster than people with normal blood clotting factors.
What is the inheritance of hemophilia?
The gene that causes the lack or deficiency in the production of clotting factor shows a sex-linked pattern of heredity. The gene that controls the production of clotting factor is located on the female (X) chromosome. Females have two X chromosomes; males have an X and a Y.
Males who inherit the defective gene on their X chromosome will have the disorder. Females who inherit the defective gene on one X chromosome and have a normal gene on the other X chromosome will be a carrier of hemophilia.
Figure 1 shows the heredity pattern of hemophilia. Each son born to a carrier mother has a 50 percent chance of having the disorder and each daughter has a 50 percent chance of being a carrier. A male with hemophilia cannot pass the disorder to his sons, but all of his daughters will be obligate carriers.
Figure 1: Heredity Pattern of Hemophilia
Normal Female Normal Male
Carrier Female Affected Male
Some female carriers have no health problems or symptoms related to carrying the hemophilia gene. These women are known as asymptomatic carriers.
Other female carriers have low factor levels that are associated with bleeding problems and are called symptomatic carriers. Symptomatic carriers may suffer excessive menstrual bleeding, bruising, nosebleeds, and bleeding after surgery, dental work, or childbirth.
Are there different types of hemophilia?
Yes. There are two main types of hemophilia: hemophilia A and hemophilia B. Hemophilia A is the most common type and affects about 85 percent of all the people with the disorder. It is also known as Factor VIII deficiency or classical hemophilia and is caused by a lack or a deficiency in the blood clotting protein Factor VIII.
Hemophilia B, known as Factor IX deficiency or Christmas disease, affects about 14 percent of all the people with hemophilia and is caused by a lack or a deficiency in the blood clotting protein, Factor IX.
The remaining 1 percent of the people with hemophilia lack or have a deficiency in the blood clotting proteins Factor V, VII, X, or XI. There are also inherited bleeding disorders involving Factor I, or fibrinogen, Factor II (prothrombin deficiency, and Factor XIII.
What is the severity of hemophilia?
The severity of hemophilia A and hemophilia B may vary depending on the amount (or level) of factor VIII or factor IX in the patient’s blood. Normal blood clotting activity levels of Factor VIII and Factor IX range between 50 percent and 200 percent, where 100 percent is the average level in the unaffected person. Hemophilia may be severe, moderate, or mild.
Severe. People with severe hemophilia have Factor VIII or Factor IX clotting activity levels less than 1 percent. About 43 percent of all the people with hemophilia are classified as severe. They often suffer frequent (weekly) internal bleeding episodes into joints, muscles, and tissues after injury or for no apparent reason. They are at risk for bleeding after dental work, surgery, and trauma.
Moderate. People with moderate hemophilia have Factor VIII or Factor IX clotting activity levels between 1 percent and 5 percent. Just like people with severe hemophilia, people with moderate hemophilia are at risk for bleeding after trauma and injury. They also may suffer spontaneous bleeding episodes, but they usually occur less frequently (monthly) than in people with the severe form of the disorder. Moderate hemophilia occurs in about 25 percent of all the people with hemophilia.
Mild. People with mild hemophilia have Factor VIII or Factor IX clotting activity levels between 6 percent and 50 percent. Bleeding problems usually only occur with major injuries, surgery, or tooth extractions. Mild hemophilia may go undetected until bleeding occurs after surgery or trauma. About 32 percent of the patients with hemophilia are classified as mild.
How is hemophilia treated?
Hemophilia is treated with factor replacement therapy. The therapy involves the intravenous infusion of blood clotting products to replace the missing or deficient protein needed for the blood to clot. Infusions must be given as soon as possible after the start of bleeding.
Alternatively, the patient can take regular doses of factor, whether they need to or not, as a preventative treatment. This preventative treatment method is called prophylaxis and is prescribed in order to prevent patients with hemophilia from getting spontaneous bleeds and to protect their joints from damage.
Optimal care for a patient with hemophilia can be found at a Comprehensive Hemophilia Treatment Center (HTC). These are state or federally designated centers and comprise a medical team including a physician, nurse, social worker, and physical therapist – all experienced in the care of patients with bleeding disorders. Additionally, there is usually a physician associated with the center who is trained in infectious diseases, including HIV and HCV. The HTC team will also work with experienced dentists, oral surgeons, orthopedic surgeons, obstetrician/gynecologists, and psychologists/psychiatrists.
Complications of Treatment?
Before 1965, hemophilia was treated with a slow transfusion of whole blood or fresh frozen plasma, which required long visits to the hospital emergency room. In 1965, a plasma extract called cryoprecipitate became available. Cryoprecipitate made the treatment of Hemophilia A much easier and more effective because less fluid had to be transfused into the patient.
By the early 1970s, clotting factor for Hemophilia A and B became available in a concentrated, freeze-dried form. This innovation made it possible for patients to self-infuse at home, work, and school. It significantly improved quality of life and increased life expectancy from 11 years in 1931 to 60 years in 1980.
However, because the clotting factor was made from the blood of many donors, the majority of those with hemophilia were infected with hepatitis B and C viruses (HBV and HCV) and with the human immunodeficiency virus (HIV), the virus that causes AIDS. This occurred before the risk of disease transmission in blood products was recognized and preventative measures taken. Since 1987, no persons with hemophilia have become HIV positive from clotting factor. Blood donors are now screened for risk of HIV, HBV and HCV. Blood is presently tested for the virus, and blood products now undergo manufacturing processes that have been shown to be effective in viral inactivation and pathogen removal.
In 1992, the first recombinant DNA derived clotting factor for use in persons with hemophilia A was approved by the U.S. Food and Drug Administration (FDA).
What are the complications of hemophilia?
The most common complication of hemophilia is joint damage that can occur when there is bleeding into the joints. Joint bleeds cause the majority of pain and discomfort for a person with hemophilia. Repeated joint bleeds into the knees, elbows, ankles, shoulders, and hips can lead to chronic swelling and later, deformity. Many people with hemophilia suffer disabling arthritis, and in severe instances, will need joint replacement surgery.
Other major complications range from the psychological impact of a chronic disease on children, adolescents, and their families as well as the fear of life threatening cerebral bleeds. In addition, patients develop antibodies (inhibitors) to the coagulation factors that are used to prevent bleeding. There are also life-long concerns about availability, cost, and purity of replacement factor products.
Is there a cure for hemophilia?
No. There is no cure for hemophilia at this time.
What is von Willebrand Disease?
von Willebrand Disease (vWD) is an inherited bleeding disorder with similarities to hemophilia. About 1.3% of the population is believed to have the gene. vWD is caused by a decreased or defective function of a protein called von Willebrand factor (vWF), which is necessary for normal blood clotting. The disease equally affects men and women. Because the gene is located on an autosomal chromosome, rather than a sex-linked X chromosome, both men and women pass the gene to their offspring.
Are there different types of von Willebrand disease?
Yes, von Willebrand disease is classified into three subtypes.Types I and III demonstrate quantitative abnormalities in the vW proteins, whereas Type II shows a qualitative abnormality. Type I is the most common form of vWD, accounting for at least 70% of all cases.Type I is also the most difficult to diagnose definitively because the three factors measured may all be at borderline levels in a patient with clinical disease.
The type and severity of symptoms a person with vWD has depends on the quality of vWF in the blood. Symptoms include excessive bleeding from the gums and from cuts, nosebleeds, and in women, excessive menstrual bleeding. In the most severe forms, deep bleeding into joints and muscles occur.
A person with mild vWD may be treated with an intravenous or intranasal medicine called desmopressin or DDAVP to boost their factor VIII and vWF levels. Persons with more severe vWD may require transfusions of a von Willebrand-containing blood product such as Humate P. There is a recombinant form of von Willebrand protein presently in the investigational clinical trial process.
Are there other types of hemophilia?
There are other bleeding disorders that are inherited. One is Factor XI deficiency which is sometimes called Hemophilia C. Factor XI deficiency is autosomally inherited. The bleeding associated with this deficiency occurs mostly with surgery or trauma. It may not be recognized until later in life. Another bleeding disorder is called Parahemophilia and that is Factor V deficiency. It is uncommon and someone who is severely affected would have inherited a gene from both parents. Current treatment of factor XI and V deficiency is with plasma infusion.
There is also a factor VII deficiency. Factor VII deficiency varies in its bleeding manifestations and ranges from severe bleeding to no bleeding. Factor VII deficiency can be treated with a recombinant activated FVII, prothrombin complex concentrates (PCCs) that are rich in factor VII, or by plasma infusion. Factor X and II deficiency are extremely uncommon but can be treated with prothrombin complex concentrates or plasma infusion.
Factor XIII deficiency can occurs if a person inherits a gene from both parents. These patients can have life threatening bleeding and the bleeding is often delayed in appearance. There is a plasma derived factor XIII concentrate as well as a recombinant product, available but both are,investigational.
There is an inherited deficiency or abnormality of fibrinogen. This is called afibrinogenemia or hypofibrinogenemia and dysfibrinogenemia. Patients with these disorders can have bleeding. Patients with dysfibrinogenemia can also have too much clotting as a problem. The fibrinogen concentrate was just recently approved for use in the USA.
Platelets are another component of the blood that participate in hemostasis or control of bleeding. These cellular particles will help plug an area of bleeding and support the coagulation system. An abnormality of platelets can cause bleeding that is similar to von Willebrand disease. Treatment is sometimes effective with DDAVP which is also used to treat von Willebrand disease. If ineffective, treatment with platelet transfusions may be necessary.
Don’t only men get bleeding disorders?
It was initially recognized that men with hemophilia have severe life-threatening and life shortening bleeding episodes with severe crippling. Women that carry the hemophilia gene may also manifest bleeding symptoms but not as severe. A concern that has arisen is that women who carry hemophilia or who have other bleeding disorders may manifest it only as menorrhagia, which is the medical term for heavy menstrual periods. It is hoped that if these women are identified before they have surgery then measures can be used to protect them from excessive bleeding with hysterectomies or other surgeries, or even avoid a hysterectomy altogether.
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