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| DiseaseID |
HGD5 |
| Genetic
Disorder |
Hemophilia A
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| Gene
Name |
factor VIII gene |
| Description |
Hemophilia A is a hereditary blood disorder, primarily affecting males, characterized by a deficiency of the blood clotting protein known as Factor VIII that results in abnormal bleeding. Babylonian Jews first described hemophilia more than 1700 years ago; the disease first drew widespread public attention when Queen Victoria transmitted it to several European royal families. Mutation of the HEMA gene on the X chromosome causes Hemophilia A. Normally, females have two X chromosomes, whereas males have one X and one Y chromosome. Since males have only a single copy of any gene located on the X chromosome, they cannot offset damage to that gene with an additional copy as can females. Consequently, X-linked disorders such as Hemophilia A are far more common in males. The HEMA gene codes for Factor VIII, which is synthesized mainly in the liver, and is one of many factors involved in blood coagulation; its loss alone is enough to cause Hemophilia A even if all the other coagulation factors are still present.
Treatment of Hemophilia A has progressed rapidly since the middle of the last century when patients were infused with plasma or processed plasma products to replace Factor VIII. HIV contamination of human blood supplies and the consequent HIV infection of most hemophiliacs in the mid-1980s forced the development of alternate Factor VIII sources for replacement therapy, including monoclonal antibody purified Factor VIII and recombinant Factor VIII, both of which are used in replacement therapies today.
Development of a gene replacement therapy for Hemophilia A has reached the clinical trial stage, and results so far have been encouraging. Investigators are still evaluating the long-term safety of these therapies, and it is hoped that a genetic cure for hemophilia will be generally available in the future
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| Symptoms |
Bruising Spontaneous bleeding Bleeding into joints and associated pain and swelling Gastrointestinal tract and urinary tract hemorrhage Blood in the urine or stool Prolonged bleeding from cuts, tooth extraction, and surgery
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| Causes |
Hemophilia A results from a deficiency (lack) of clotting factor VIII.
The disorder is caused by an inherited X-linked recessive trait, with the defective gene located on the X chromosome. That means the disorder occurs primarily in males. Females carry two copies of the X chromosome, so if the factor VIII gene on one chromosome doesn't work, the gene on the other chromosome can do the job. Males, however, carry only one X chromosome, so if the factor VIII gene on that chromosome is broken, they will have hemophilia A.
If a woman has a defective factor VIII gene, she is considered a carrier. The gene can be passed down to her children. Half of the male babies born from women who carry the defective gene have a 50% chance of developing the disease. Half of the female babies born from women who have the defective gene have a 50% chance of being carriers. All female children of men with hemophilia carry the defective gene.
The severity of symptoms can vary. Severe forms become apparent early on. Bleeding is the main symptom of the disease and sometimes, though not always, occurs if an infant is circumcised. Additional bleeding problems are seen when the infant starts crawling and walking.
Mild cases may go unnoticed until later in life when they occur in response to surgery or trauma. Internal bleeding may happen anywhere, and bleeding into joints is common. Risk factors are a family history of bleeding and being male. |
| Diagnosis |
Many blood clotting tests are performed if the person tested is the first one in the family to have a bleeding disorder. Once the defect has been identified, other family members will need less testing to diagnose the disorder.
Tests include:
Prolonged PTT Normal prothrombin time Normal bleeding time Normal fibrinogen level Low serum factor VIII activity
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| Treatment |
Standard treatment involves replacing the missing clotting factor. The amount of factor VIII concentrates needed depend upon the severity of bleeding, the site of the bleeding, and the size of the patient.
Mild hemophilia may be treated with desmopressin (DDAVP), which helps the body release factor VIII that is stored within the lining of blood vessels.
To prevent a bleeding crisis, people with hemophilia and their families can be taught to give factor VIII concentrates at home at the first signs of bleeding. People with severe forms of the disease may need regular preventative treatment.
Depending on the severity of the disease, DDAVP or factor VIII concentrate may be given prior to dental extractions and surgery to prevent bleeding.
Immunization with Hepatitis B vaccine is necessary because of the increased risk of exposure to hepatitis due to frequent infusions of blood products.
Patients who develop an inhibitor to factor VIII may require treatment with other clotting factors such as factor VIIa, which can aide clotting even in the absence of factor VIII. |
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