Hemophilia the Most Common Genetic

Hemophilia

The most common genetic bleeding disorder is von Willebrand Disease, which affects roughly 3% of the world's population including all genders and races, and which is determined by a gene on chromosome 12, although occasionally it occurs as a new mutation (Curry 2004). Other inherited bleeding disorders, such as platelet or fibrinogen dysfunctions are extremely rare, and 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, but 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 1:5,000 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 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 be 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 is completely missing, which essentially 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 keeps it from losing too much blood, which can be life threatening and/or cause damage to the internal organs (Hemophilia 2006). These clotting factors are proteins in the blood that work with platelets to help the blood to clot, thus when blood vessels are damaged, the clotting factors help the platelets adhere together to basically plug cuts and breaks at the injury site (Hemophilia 2006).

The two main types of hemophilia are: hemophilia A - clotting factor VIII is low or missing, and hemophilia B - 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). Hemophilia is determined to be mild, moderate or severe by the amount of clotting factor in the blood; approximately 7 out of 10 of those with hemophilia A have the severe form (Hemophilia 2006).

While normal people 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 that is 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 the sex of the baby (Hemophilia 2006). Chromosomes are paired: females have two X chromosomes and 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 on to her children: there is a one in two chance her son will have hemophilia, and one in two chance that 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). Moreover, some males with hemophilia are born to mothers who are not carriers, this happens when a random change or mutation occurs in the gene as it is passed to the baby (Hemophilia 2006).

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, and usually the first sign is heavy bleeding from an accident, surgery or a dental procedure. Children with mild to moderate hemophilia may not have 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 they are 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; joint becomes swollen and hot to touch with pain during movement; swelling continues as bleeding continues with loss of joint movement; bleeding slows after several days when the joint is full of blood; and if not treated can lead to disabling arthritis in the joints (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 the blood to clot; whether the blood has low levels of any of the clotting factors; whether one of the factors is missing; and what type of hemophilia is present and 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 of hemophilia, it is important to distinguish hemophilia A from hemophilia B. because the treatments are different (Hemophilia 2006).

The primary treatment for hemophilia is replacement therapy, in which concentrates of the clotting factor are infused or injected directly into the blood stream: factor VIII for hemophilia A and factor IX for hemophilia B, and can be used to prevent bleeding or stop bleeding on an as-needed basis (Hemophilia 2006). Although replacement therapy is usually not need for mild hemophilia, desmopressin (does not help in hemophilia B) is sometimes given to raise the body's levels of factor VIII, however because its effects diminish with chronic use, it is applied only in certain situations, such as prior to dental procedures (Hemophilia 2006). Moderate hemophilia is treated only when bleeding occurs, although treatment may also be given to prevent bleeding prior to participating in an activity. In cases of severe hemophilia, long-term or shorter term preventive therapy is needed to prevent bleeding that could cause permanent damage to the joints, muscles, or other parts of the body however some individuals receive treatment only when bleeding occurs (Hemophilia 2006). It is crucial to get treatment as soon as possible if bleeding occurs because delay can result in serious complications.

The clotting factor concentrates used in replacement therapy come from two sources: blood from human donors and lab produced clotting factors called recombinant factors. Clotting factor concentrate infusions must be given once daily or more frequently when treatment has begun because half of the activity of factor VIII is gone in 8-12 hours and half of the activity factory IX is gone in 12-24 hours (Hemophilia 2006). The amount of clotting factor given depends on: the type of hemophilia, the bleeding site and severity of the bleeding, body weight, and whether the individual has developed an antibody that neutralizes the activity of the clotting factor (Hemophilia 2006). Antibodies to clotting factor develop in about 20% of people with severe hemophilia A, and about 1% of those with hemophilia B. When antibodies develop, larger doses may be used or physicians may try different sources of the clotting factor (Hemophilia 2006). The viruses that cause AIDS (HIV) and hepatitis can be carried in clotting factors however there have been no documented cases of such transmission in about ten years. Prevention of viruses can be prevented by: careful screening of donors; testing of donated blood products; treating donated blood products with a detergent and heat to destroy viruses (Hemophilia 2006). Both preventive and as-needed therapy can be administered at home, thus resulting in quicker treatment, fewer doctor or emergency room visits, and less costs. Vein access devices can be surgically implanted to allow easier access to a vein however infections can result from such devices (Hemophilia 2006).

All patients with bleeding disorders may benefit at times from using aminocaproic acid, an oral antifibrinolytic medication that helps stabilize clots (Curry 2004). Aminocaproic acid is the only product available in the United States in oral form, however it is not user-friendly, with dosing every 6 hours around the clock for up to 14 days and only one tablet dose size available, thus a 55 pound child would need to take 5 large tablets every 6 hours or an unpleasant tasting liquid (Curry 2004). Side effects of aminocaproic acid include nausea and vomiting, and it should not be used with bleeding in the urinary tract in order to avoid intra-renal obstruction due to clots (Curry 2004). The oldest, easiest and least expensive treatment is RICE: Rest, Ice, Compression, and Elevation, which can be used alone to treat minor bumps and bruises or along with factor for more severe bleeding episodes (Curry 2004). Individuals with bleeding disorders do not bleed more than other people, they just bleed longer (Curry 2004). Acetaminophen is recommended for pain and fever, since people with bleeding disorders should avoid aspirin and ibuprofen due to those medications' effects on hemostasis (Curry 2004). If an anti-inflammatory medication must be used, then choline magnesium trisalicylate is recommended; the newer cox2 inhibitors are also reasonably safe and effective (Curry 2004). Herparin and warfarin therapy are also contraindicated (Curry 2004).

Counseling that promotes competence and hope concerning HIV/HCV management, identifies personal life goals, and increases social support outside of the family are important elements of good therapy (Taylor 2004). Due to advances in technology, adults and families with children with hemophilia can weigh safety issues against the benefits of new, largely synthetic, blood products (Taylor 2004). Social workers can assist clients in evaluating new information and developments, and this partnered approach to disease management is congruent with the increasing demand for mutual accountability (Taylor 2004). The shift to community care allows the social worker opportunities to enhance patient self-determination by working with self-help organizations in a consumer participatory model, and to help them develop their own self-help initiatives (Taylor 2004).

During the 1980's, the hemophilia community was hit hard when blood products carrying the AIDS virus caused the death of more than 179 young recipients under the age of 13 years (Schaefer 1999). Ryan White and Ricky Ray were two youths who contracted AIDS from their hemophilia treatments. In 1998, the Ricky Ray Law was signed into law which provides payment of $100,000 to individuals with hemophilia who contracted HIV through contaminated blood products (Schaefer 1999).

In response to the HIV virus transmission, researchers began working to develop a non-plasma derived clotting factor. When the DNA recombinant protein became available in 1992, the first DNA-cloned recombinant factor VIII became commercially available (Schaefer 1999).

Many hemophilia patients have survived infection with HIV and are now considered 'chronic,' which is a testament to ongoing collaborative clinical research (Schaefer 1999). Recombinant factor VIII and factor IX products are not derived from human plasma, and are ideally suited for patients who have never encountered human blood product, and for the immune deficient HIV-infected patients who wish to avoid further contact with the potential risks of human plasma-derived products (Schaefer 1999). Due to expense and scarcity, patients may also receive 'old-fashioned' non-recombinant products that are fractionated from human plasma, however although blood products are now treated to be free of HIV virus, they continue to carry some risks of hepatitis, Creutzfeldt-Jakob Disease, parvovirus, and other unknown viruses (Schaefer 1999).

Before the use of home-infusion therapy, children with hemophilia often experienced frequent emergency department visits and extended hospital stays, which resulted in numerous missed days of school and prolonged separation from their families (Noll 2003). Yet, despite advances in treatment, children with hemophilia continue to miss more school than their peers, which may put them at a disadvantage both academically and socially (Noll 2003). Moreover, even when they are in school, they are often not allowed to participate in certain activities, which may interfere with their development of social skills, self-esteem and friendships (Noll 2003).

A study published in the August 2003 issue of the Journal of Developmental and Behavioral Pediatrics by Robert B. Noll found that children with hemophilia seem to experience some difficulties with emotional well-being when compared with peers of the same gender, race, and age with a chronic illness (Noll 2003). Noll's study also found that children with sickle cell disease, cancer and juvenile rheumatoid arthritis did not have difficulties with emotional well being (Noll 2003). Noll suggest that the difference may be due to the threat of HIV for the children with hemophilia that makes them more vulnerable (Noll 2003). Another study examining the effects of HIV on children with hemophilia reported that "children who were HIV positive exhibited more difficulties in the area of adaptive, emotional, and behavioral functioning than children who were HIV negative" (Noll 2003).

According to the National Institutes of Health, hepatitis C virus is the most common chronic blood-borne infection in the United States, infecting approximately 2% of the U.S., many of whom are chronically infected and may not be aware of their infection because they are not clinically ill (Brooks 2003). Recipients of dotting factor concentrated prepared from plasma pools posed a high risk for HCV infection until procedures to inactivate viruses, including HCV, were introduced in 1985 (factor VIII) and 1987 (factor IX) (Brooks 2003). Mirella Vasquez. Brooks reported in the July 2003 issue of Nursing Forum that the highest prevalence of infection is found among those with large or repeated exposure to blood or blood-containing products. Individuals who were treated with products made before 1987 have a HCV infection prevalence of 87%, and an estimated 75% of those with hemophilia who are over 12 years of age have chronic HCV infections, with up to one third of these co-infected with HIV (Brooks 2003).

There is very little information available concerning HCV infections of partners of hemophilia patients infected with HCV (Brooks 2003). In 1998, the Centers for Disease Control established the Universal Data Collection to serve as a national blood safety monitoring system for people with bleeding disorders who receive treatment with these products (Brooks 2003). Maryland Pao reports in the August 2005 issue of the Journal of the American Academy of Child and Adolescent Psychiatry that the clinical presentation of HIV encephalopathy may vary with age of infection and mode of transmission (Pao 2005). Writes Pao, "In children and adolescents infected through blood transfusion, encephalopathy generally presents later and follows a more indolent course" (Pao 2005). While encephalopathy is uncommonly an AIDS-defining illness for hemophiliacs, in as many as 21% of vertically HIV-infected children, encephalopathy can present and contribute significant morbidity and mortality as an AIDS-defining illness even when the child is not severely immuno-compromised (Pao 2005).