Genetic Diseases: Hemophilia

1. Genetic Diseases: Hemophilia By: Chance Parrish

2. What is hemophilia? • Hemophilia is a sex-linked genetic disorder passed down on the X chromosome* that affects the rate of coagulation (clotting) and the sustainability of clots that do form. • Hemophilia is the deficiency in certain clotting factors, which determine the ability of clots to form. There are three types, the first two of which are much more common than the third. Hemophilia A and B affect clotting factors VIII and IX, respectively, while Hemophilia C affects clotting factor XI. • *It should be noted that Hemophilia C is recessive and NOT sex-linked, but autosomal.

3. Discovery and history • Hemophilia is recorded in cases as far back as in the early C.E. centuries after rabbis picked up on the trend of boys who died of blood loss after circumcision having brothers that did the same. This was most likely Hemophilia C due to reasons that will be explained. • In Prince Leopold, the son of Queen Victoria, hemophilia became one of the first widely publicized diseases. Leopold’s hemophilia case made the disease a forefront of medical inquiry. • Hemophilia B was first recorded in Stephen Christmas, leading to its nickname, the Christmas disease.

4. Genetic Background • Hemophilia A and B are sex-linked forms of hemophilia and are passed down on the X chromosome. The disease will show in the son of a mother that carries the disease on either one or both X chromosomes and only in women that have the disease on both X chromosomes (although this is extremely rare). • Hemophilia C is autosomal recessive and appears most commonly in Ashkenazic Jews. • All forms of hemophilia are recessive.

5. Hemophilia A: Symptoms and Treatments • Hemophilia A is related to the deficiency in clotting factor VIII and is the most common of the hemophilia diseases. • Hemophilia A symptoms can appear in females that are hybrid for the hemophilia gene, but this rarely happens and the symptoms are extremely watered down. • There are three levels of hemophilia A: severe, moderate, and mild. Severe is classified as having below 1% the normal clotting factor. Moderate have between 1% and 5% normal clotting factor. Mild has between 5% and 40% clotting factor. • Bleeding occurs in open wounds most commonly, but also in joints, muscles, the brain, and the digestive system. • Recombinant (genetically engineered) factor VIII is now one of the most common treatments for hemophilia A. Desmopressin is another drug that is used to treat hemophilia A.

6. Hemophilia B • Hemophilia B is characterized by the deficiency of clotting factor IX. • This disease was the strand of hemophilia that ran in the royal lines of many of the European noble families. • Hemophilia B is the middle child in terms of how common it is among the three strands. • This disease exhibits the same symptoms of hemophilia B. However, it can be treated in other ways. Recombinant factor IX is used instead of recombinant factor VIII in the treatment, but another aid is to use tranexamic acid to slow the rate of bleeding in those undergoing surgical procedures.

7. Hemophilia C • Hemophilia C is the oddball of the hemophilia world. It is autosomal, so it is passed on neither the X nor the Y chromosomes. • Hemophilia C is characterized by deficiency of coagulation factor XI, but it exhibits similar symptoms to hemophilia A and B. • The symptoms, however, do not occur as often as in hemophilia A and B and are set apart by the void of bleeding in joints. • Also, hemophilia C is treated far less than the other two strands mostly due to its lessened severity. Treatment is usually only needed in patients undergoing surgery, in which case recombinant factor XI is used to lessen symptoms.