Hemophilia: Causes, Symptoms, Treatments, and Complications

Introduction to Bleeding Disorders and Hemophilia

The most common genetic bleeding disorder is von Willebrand Disease, which affects roughly 3% of the world's population across all genders and races. It is determined by a gene on chromosome 12, although it occasionally arises as a new mutation (Curry 2004). Other inherited bleeding disorders, such as platelet or fibrinogen dysfunctions, are extremely rare; most have autosomal recessive inheritance but can also arise from new mutations (Curry 2004). Children may have bleeding problems that are not inherited disorders, such as idiopathic thrombocytopenia purpura (ITP), which is typically a transient autoimmune platelet destruction process and may occur secondarily due to bone marrow suppression from chemotherapy (Curry 2004). However, more famous — though less common — are the hemophilias: hemophilia A and hemophilia B (Curry 2004).

There are approximately 18,000 people with hemophilia in the United States, roughly 1 in 5,000 male live births (Curry 2004). Hemophilia may be mild (5–49% factor activity), with bleeding episodes after trauma or surgery; moderate (1–5% factor activity), with bleeding after stress or overuse injury to joints or muscles; or severe (less than 1% factor activity), with all of the above plus possible spontaneous bleeding episodes into joints or muscles (Curry 2004). Hemophilia is a chronic condition characterized by a deficiency of clotting factor — usually factor VIII — and is an X-linked genetic disease that affects males almost exclusively (Noll 2003). While external bleeding is easily controlled, internal bleeding, most commonly into the joints and muscles, can result in severe complications (Noll 2003). Although internal bleeding is frequently spontaneous, it can also occur as the result of trauma or stress (Noll 2003). The immediate results of bleeding into the joints are severe pain, swelling, and interruption of activity; however, long-term results can include chronic arthritis or permanent loss of function in the affected joint (Noll 2003). Bleeding that occurs in the central nervous system can lead to neural injury or death (Noll 2003).

Hemophilia is due to either a low level of one of the clotting factors or a clotting factor that is completely missing, which means that it takes a long time for the blood to clot after an accident or injury (Hemophilia 2006). The clotting process — also called blood coagulation — is the body's response to bleeding that prevents it from losing too much blood, which can be life-threatening and cause damage to internal organs (Hemophilia 2006). Clotting factors are proteins in the blood that work with platelets to help blood clot; when blood vessels are damaged, the clotting factors help platelets adhere together to plug cuts and breaks at the injury site (Hemophilia 2006).

Types, Severity, and Genetic Transmission

The two main types of hemophilia are hemophilia A — in which clotting factor VIII is low or missing — and hemophilia B — in which clotting factor IX is low or missing. Hemophilia may also occur when antibodies to these clotting factors form and block their function (Hemophilia 2006). Hemophilia A is also known as classic hemophilia and factor VIII deficiency; hemophilia B is also known as Christmas disease and factor IX deficiency (Hemophilia 2006). The severity of hemophilia is determined by the amount of clotting factor present in the blood; approximately 7 out of 10 people with hemophilia A have the severe form (Hemophilia 2006). While normal individuals have a factor VIII activity of 100%, those with severe hemophilia A have a factor VIII activity of less than 1% (Hemophilia 2006).

Hemophilia is an inherited disorder caused by a defect in the genes that determine how the body makes blood clotting factors VIII and IX, which are located on the X chromosomes that determine biological sex (Hemophilia 2006). Chromosomes are paired: females have two X chromosomes, while males have one X and one Y chromosome. If a female has a defective gene for factor VIII or factor IX on one of her X chromosomes, she is a "carrier" and can pass the defective gene to her children. There is a one in two chance her son will have hemophilia, and a one in two chance her daughter will be a carrier (Hemophilia 2006). A male who has hemophilia cannot pass the disorder to his sons; however, all of his daughters will be carriers. Although very rare, a female may be born with hemophilia if her father has hemophilia and her mother is a carrier (Hemophilia 2006). Additionally, some males with hemophilia are born to mothers who are not carriers; this occurs when a random change or mutation arises in the gene as it is passed to the baby (Hemophilia 2006).

Signs, Symptoms, and Diagnosis

The major signs and symptoms of hemophilia are bleeding and bruising. Internal bleeding is common in cases of severe hemophilia and, if not treated promptly, can lead to damaged joints, muscles, or other parts of the body (Hemophilia 2006). Children with very mild hemophilia may not have noticeable symptoms for years; usually the first sign is heavy bleeding from an accident, surgery, or a dental procedure. Children with mild to moderate hemophilia may not show any signs or symptoms at birth, while males with severe hemophilia may experience heavy bleeding after circumcision (Hemophilia 2006).

Usually, the first signs in most children are heavy bruising and bleeding from the gums when they cut their first teeth, bumps and bruises from frequent falls when learning to walk, and swelling and bruising from bleeding in the joints, soft tissue, and muscles (Hemophilia 2006). In older children and adults, the most common symptoms are bleeding in the joints; bleeding and bruising in the soft tissue and muscles; bleeding in the mouth from a cut, bite, or loss of a tooth; spontaneous nosebleeds; blood in the urine; and blood in the stool (Hemophilia 2006). Although bleeding can occur in any joint, it is most common in the knees, elbows, and ankles. Symptoms of joint bleeding include tightness in the joint with no real pain; tightness and pain with no visible signs of bleeding; the joint becoming swollen and hot to the touch with pain during movement; swelling that continues as bleeding continues, with loss of joint movement; bleeding that slows after several days when the joint is full of blood; and, if untreated, the potential for disabling arthritis (Hemophilia 2006).

The symptoms of bleeding in the brain — which can occur after a simple bump on the head — include long-lasting painful headaches, vomiting, behavioral changes, lethargy, sudden weakness of limbs, neck pain or stiffness, double vision, difficulty walking, and convulsions or seizures (Hemophilia 2006).

Blood tests are used to determine how long it takes for blood to clot, whether the blood has low levels of any clotting factors, whether one of the factors is missing, and what type of hemophilia is present along with its severity (Hemophilia 2006). Infants with severe hemophilia are generally diagnosed during the first year of life; however, individuals with milder forms may not be diagnosed until adulthood (Hemophilia 2006). While the bleeding problems are the same for both types, it is important to distinguish hemophilia A from hemophilia B because the treatments differ (Hemophilia 2006).