TITLE: Hemophilia A

Name: Stephanie Isola
Date: May 18, 2010

The purpose of this paper is to provide an in-depth examination of the genetically transmitted disorder hemophilia A. Hemophilia A is caused by a mutated gene, which is predominately passed down from parent to offspring. This research paper provides a thorough analysis of hemophilia A, the inheritance of the mutated gene, as well as the causes, symptoms, diagnosis, treatment, and prognosis.

Hemophilia A is a genetically transmitted blood disorder characterized by an individual’s inability to effectively control bleeding. According to the U.S. Department of Health and Human Services (2009), hemophilia A is the most common form of hemophilia and infects more than 18,000 people in the United States. The disease is inherited through the X chromosome passed down from parents to children. The chromosome has a defective gene which results in a deficiency in the blood clotting factor called factor VIII. Without a sufficient amount of factor VIII, individuals will suffer from difficulties in efficiently transforming liquid blood into solid to stop the bleeding. It is fascinating how such a slight mutation in a gene, that is most often inherited, can have ever-lasting effects on an individual’s ability everyday life.

This disease, hemophilia A, is an inherited X-linked recessive trait which means the defective gene is located on the X chromosome. Since men only have one X chromosome, any male who inherits a hemophilia A coded X chromosome will have the disease. “The Y chromosome is mainly involved in determining gender and does not contain genes for the production of clotting factor” (Massimini, 2000, pg. 182). For females to inherit the disease, they must receive a defective X chromosome from both parents. If a female only receives one defective X chromosome they will simply be carriers of the disease and their “un-defected” X chromosome will mask the defective one protecting the female from becoming a hemophiliac. And, if males do not receive the defective X chromosome from their mother, but a hemophilia A coded Y chromosome from their father they will be carriers (Zallen, 1997). Considering that males only need to inherit one defective X chromosome to contract the disease, hemophilia A is found to be much more common among men than women.

(U.S. Department of Health, 2009)

Gene Mutation
Hemophilia genes result from a genetic mutation. A mutation is a variation in the base sequence of DNA. Approximately half of hemophilia cases occur from a “single base-pair substitution mutation in the gene for coagulation factor VIII” (Laurie, Smith, & George, 2007, par. 1). This is when a single base within the DNA sequence is replaced with a different base. When this mutated DNA is copied, new strands of DNA are created containing the mutation lacking proper blood clotting factor VIII. “To be specific, about 45% of severe Hemophilia A cases are the result of a large inversion that disrupts the factor VIII gene in intron 22 and a further 1%-5% are caused by an inversion affecting intron 1” (Laurie et al, 2007, par. 4). Other mutations that are known to contribute to hemophilia genes include missense, nonsense, or frameshift mutations (Laurie et al, 2007). All of these mutations cause deficiencies in the DNA’s code for factor VIII, which can then be passed to offspring who become carriers or hemophiliacs.

(Bolton-Maggs & Pasi, 2003)

Symptoms of hemophilia A include difficulties in the ability to properly stop bleeding. Hemophilia A has different levels of symptoms which include mild, moderate, and severe. Individuals with mild hemophilia A typically only have problems with bleeding following major trauma and surgery (Mueller & Young, 2001). Those with moderate hemophilia A often have bleeding issues after an injury has occurred. And people with severe hemophiliac A, which is 60% of the hemophiliac A population, suffer from bleeding after most injuries and often have bleeding into joints and muscles (National Hemophilia Foundation, 2006). It is important to recognize that hemophiliacs bleed at the same rate as individuals with normal levels of factor VIII; however they are unable to properly stop the bleeding process.

(Kelley, 2007)

In order to stop the bleeding, hemophiliacs can use replacement therapy to substitute for the lack of factor VIII. Replacement therapy for hemophilia A comes in a few different forms. The first type is a dried, powdered clotting factor that is mixed with water (Khair, 2006). The second type is plasma factor VIII derived from donated human blood plasma. The third is a recombinant factor that is made in a laboratory and free of human blood, which is helps to prevent the transmission of human diseases (UCSF’s Children’s Hospital, 2010). All factors are injected intravenously so that they can enter the blood stream and swiftly help form necessary clots. Most infusions can be administer at home and have a “half-life of 8 hours so that repeated infusions are often necessary, especially for major trauma” (Mueller & Young, 2001, pg. 284). When treatment is not prompt, excessive bleeding will cause joints to swell with blood, which sometimes results in softened joints and arthritis. In order to avoid these types of problems, it is important seek treatment as need, which can be periodically or as often as everyday, to avoid severe bleeding episodes.

Diagnosis usually occurs because an individual suspects to have to disease due to family history or has experienced a bleeding episode. The diagnosis procedure uses blood to test to find genetic variations in DNA. One way to test for the mutation uses high-resolution melting analysis. First, DNA is amplified using polymerase chain reaction. The DNA is then denatured using high-resolution melting analysis and mixed with primers. The primers target the factor VIII exon where the hemophilia A mutation can be found. High-resolution melting analysis is a powerful and cost effective option for testing for mutations in the factor VIII gene (Laurie et al, 2007). This is just one way to sequence DNA in order to find the hemophilia A mutation. People who have a family history of the disease or have issues with blood clotting should request testing for hemophilia A.

Hemophilia A is a sex linked genetic disease that results in the lack of factor VIII. The disease ranges from mild, moderate, and severe. “About 18,000 people in the United Sates have hemophilia A. Each year, about 400 babies are born with the disorder and are usually males” (U.S Department of Health and Human Services, 2009, par. 12). The disease cannot be cured; however, there are successful treatments to help control bleeding symptoms. In order to diagnosis the disorder, individuals should consider their family history and incidents of prolonged bleeding. Genetic sequencing is currently being used to determine the exact sequence of nucleotide bases in DNA and pinpoint mutations in factor VIII, which contribute to hemophilia A. Although hemophilia A can be acquired through genetic mutations during one’s life, it is most often passed down through family lineage and at this time there is no cure to preventing the genetic passing of the mutagen disease.

Literature Cited
Bolton-Maggs, P. H., & Pasi, K. J. (2003, May 23). Haemophilias a and b. The
Lancet, 361(9371), 1801. Retrieved from ProQuest database.
Hemophilia. (2009, July). U.S. department of health and human services (http://www.nhlbi.nih.gov/health/dci/Diseases/hemophilia/hemophilia_what.html).
Hemophilia. (2010, March 10). UCSF children’s hospital (http://www.ucsfchildrenshospital.org/conditions/hemophilia/)

Kelley, L. (2007, November 27). Building bridges [Web log post]. Retrieved from
Hemablog: http://blog.kelleycom.com/2007/11/building-bridges.html
Khair, K. (2009, December). Evaluating a self infusion device for children with hemophilia. Pediatric Nursing, 18(10), 19-21. Retrieved from ProQuest database.
Laurie, A. D., Smith, M. P., & George, P. M. (2007, December). Detection of factor VIII gene mutations by high-resolution melting analysis. Clinical Chemistry, 53(12), 2211-15. Retrieved from ProQuest database.
Massimini, K. (2000). Genetic disorders sourcebook (L. L. Harris, Ed., 2nd ed.). Detroit, MI: Frederick G. Ruffner, Jr.
Mueller, R. E., & Young, I. D. (2001). Emery’s elements of medical genetics (R. Furn, Ed., 11th ed.). London: Hartcourt. (Original work published 1968)

Zallen, D. T. (1997). Does it run in the family: A consumer’s guide to DNA testing for genetic disorders. United States.