Hemophilia

Suffering an occasional cut, scratch, or bruise is a normal consequence of life. When there is damage to the skin and a blood vessel ruptures, bleeding occurs. The human body is then able to initiate a series of reactions which cause the bleeding to stop. First, platelet cells in the blood move toward and attach to the site of the wound. The platelets are further held in place by strands of fibrin. The formation of the strands is the key event in a complex series of enzymatic reactions that are still somewhat of a mystery today. Without this cascade clotting process, people would be in danger of bleeding to death from very minor injuries.

However, the scenario described above could be fatal for a person afflicted with hemophilia. The term hemophiliac, coined by the German physician Johann Schönlein (1793-1864) in 1828, is made up of Greek and Latin terms which refer to "one who loves to hemorrhage or bleed." First described by the Islamic surgeon Abu al-Qasim in the tenth century, this genetic disease has existed for several hundred years and has directly influenced history. Queen Victoria (1819-1901) had several hemophilic sons that died before they had the opportunity to become King of England. As early as the nineteenth century, scientists suspected that hemophilia may be passed from parents to offspring, or inherited. They also noticed that generally only males showed theuncontrolled bleeding that is a major symptom of the disease.

Today we know that hemophilia is caused by a small defect in a single human gene. When this particular defect occurs, as in classic or type A hemophilia,the body lacks an important protein which helps to form fibrin. This proteinis called factor VIII. About 85 percent of all hemophiliacs are missing the gene that instructs the body's cells how to produce factor VIII. Hemophilia Bis a less common type of genetic disease caused by a deficiency in another necessary protein, called factor IX. In each type of bleeding disorder, proteins are either missing or deficient and thus fibrin is not able to form. Approximately 2 out of every 10,000 males are afflicted with either type A or typeB hemophilia.

Hemophilia is a sex-linked trait because the genes for factor VIII and IX arelocated on the X sex chromosome. Female cells contain two X chromosomes andmale cells contain one X chromosome and one Y chromosome. All males inherit one factor VIII gene on the X chromosome from their mothers. If this gene is defective, the male will be hemophilic. A female, in contrast, has two factorVIII genes, one inherited from each parent. If one gene is defective but theother is not, the female will not be affected by this disease. The normal gene on the second X chromosome protects her. She will, however, carry the defective gene and may pass this gene on to her children. Generally, carrier females will pass their defective gene on to half their daughters, who will be carriers, and to half their sons, who will be hemophilic. For example, Queen Victoria was a carrier, and the genetic profile of her offspring supports this fact. Only in a very rare situation would a female acquire two defective genesand be hemophilic.

Fortunately, hemophiliacs can be treated with transfusions of concentrated factor VIII protein. This has increased the life expectancy of some hemophiliacs. The protein concentrate can be prepared by combining volumes of blood donated from many humans with normal clotting blood. However, this methodusually spreads viral diseases which were present in the original donated blood. Many hemophiliacs are chronically infected with these viruses which include the virus that causes AIDS and hepatitis. In fact, in the early to mid-1980s, over 90% of the people with severe hemophilia contracted the AIDS virus through contaminated human blood plasma. Only recently has a process been invented where certain viruses, including the AIDS virus, can be detected in theblood supply. Cow and pig blood have also been concentrated and used as a therapy, since these animals have higher concentrations of factor VIII than humans. Transfusion reactions and other problems have caused a decline in the useof animal-derived factor VIII.

In the early 1980s, a completely new way of making factor VIII was discovered. Scientists from several research companies have been able to make the factor VIII protein by isolating the normal gene and inserting this human gene into hamster cells. The hamster cells then produce large amounts of pure factorVIII protein. The protein is then harvested and used as a therapy for hemophiliacs. This process is called genetic engineering. In addition to eliminating many of the side effects associated with previous factor VIII therapies (for example, complications from bleeding and from transfused blood and blood products that may be contaminated with a virus), a gene therapy approachpromises to provide a permanent programming of cells to make clotting factor.Studies in mice has shown the process to be effective, and clinical trials in humans are on the horizon. According to the World Federation of Hemophilia,the cure for hemophilia using gene therapy is imminent.

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