$Unique_ID{BRK03810} $Pretitle{} $Title{Hemophilia} $Subject{Hemophilia Classical Hemophilia Christmas Disease AHF Deficiency AHG Deficiency Hemophilia A, also known as Factor VIII Deficiency Hemophilia B, also known as Factor IX Deficiency Hemophilia C, also known as Factor XI Deficiency Von Willebrand Disease (Vascular Hemophilia) Factor IX Deficiency Thrombasthenia } $Volume{} $Log{} Copyright (C) 1985, 1986, 1990, 1992, 1993 National Organization for Rare Disorders, Inc. 39: Hemophilia ** IMPORTANT ** It and is possible that the main title of the article (Hemophilia) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Classical Hemophilia Christmas Disease AHF Deficiency AHG Deficiency Hemophilia A, also known as Factor VIII Deficiency Hemophilia B, also known as Factor IX Deficiency Hemophilia C, also known as Factor XI Deficiency Information on the following diseases can be found in the Related Disorders section of this report: Von Willebrand Disease (Vascular Hemophilia) Factor IX Deficiency Thrombasthenia General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Hemophilia is a rare inherited blood clotting (coagulation) disorder caused by inactive or deficient blood proteins (usually factor VIII). Factor VIII is one of several proteins that enable the blood to clot. Hemophilia is found in males almost exclusively and can be classified as mild, moderate or severe. The level of severity is determined by the percentage of active clotting factor in the blood (normal percentage ranges from 50 to 150 percent). People who have severe hemophilia have less than 1 percent of active clotting factor in their blood. There are 3 major types of Hemophilia: Hemophilia A (also known as classical hemophilia, Factor VIII deficiency or antihemophilic globulin [AHG] deficiency); Hemophilia B (Christmas disease or factor IX deficiency); and Hemophilia C (factor XI deficiency). Von Willebrand Disease and other rare blood clotting disorders have similar symptoms but are not usually called hemophilia. Symptoms Hemophilia is a rare inherited blood clotting disorder. The most serious symptom of Hemophilia is uncontrolled internal bleeding that can begin spontaneously without any apparent cause. Internal bleeding may cause permanent damage to joints and muscles. A hemophiliac bleeds for a longer period of time than people who have the normal percentage of active clotting factors in their blood. External bleeding can usually be controlled and minor cuts can be treated as normal. Bruises and trauma can trigger episodes of serious internal bleeding in people with Hemophilia. Causes Hemophilia is inherited as an X-linked recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. A male with Hemophilia cannot pass the disease on to his sons. All of his daughters will be genetic carriers and can pass the Hemophilia gene on to their children. Although most people with Hemophilia have a family history of the disease, as many as one-third of the new cases are found in persons without a family history of Hemophilia. Some of these cases may result from new genetic mutations (spontaneous). Affected Population Hemophilia is a rare inherited blood clotting disorder that affects approximately 20,000 males in the United States. This number does not include many mild cases that may remain undiagnosed. These are generally discovered following major trauma or surgery. Hemophilia occurs in one out of 4,000 male newborns. Medical advances in treatment have enabled people with Hemophilia to reach a near-normal life expectancy. Related Disorders Symptoms of the following disorders can be similar to those of Hemophilia. Comparisons may be useful for a differential diagnosis: Von Willebrand Disease (Vascular Hemophilia) is a rare inherited disorder that affects coagulation or clotting of the blood. Symptoms are usually noticed during infancy or early childhood. This disorder is characterized by prolonged bleeding most frequently from the nose or the gastrointestinal tract. Blood clotting time is also abnormal. Delayed clotting time is due to a deficiency of factor VIII (clotting protein) and "von Willebrand factor protein." The platelets in the blood may have abnormal structural features as well. People with Von Willebrand Disease may bruise easily and bleed excessively after injury, menstruation, childbirth, surgery, and some dental procedures. (For more information on this disorder, choose "Von Willebrand" as your search term in the Rare Disease Database). Factor IX Deficiency is a very rare inherited disorder of blood clotting or coagulation. This disorder is characterized by severe and prolonged hemorrhaging. In very severe cases there may be joint pain and bone deformities. Factor IX Deficiency mimics Hemophilia A. Males are most frequently affected by this disorder. Bleeding episodes may occur spontaneously or because of injury. Hemorrhages may occur at or near the surface of the skin or internally. (For more information on this disorder, choose "Factor IX Deficiency" as your search term in the Rare Disease Database). Thrombasthenia is a rare inherited disorder of blood coagulation. This disorder is characterized by hemorrhaging that is caused by the abnormal function of platelets in the blood. A variety of genetic disorders may cause thrombasthenia. Children with thrombasthenia tend to bleed easily and profusely especially after injury and during surgery. Easy bruising may occur and large purplish spots may appear on the skin due to bleeding beneath the skin. (For more information on this disorder, choose "Thrombasthenia" as your search term in the Rare Disease Database). Therapies: Standard There is no cure for Hemophilia. Internal bleeding may be controlled with the intravenous administration of a blood-clotting factor, generally Factor VIII. The clotting factor remains active in the blood for only a short time. Repeated administration of blood clotting factor is required each time internal bleeding occurs to avoid permanent damage. This therapy is necessary throughout the life of the patient with Hemophilia. The drug desmopressin (Stimate) is used for treatment of moderately severe cases of Hemophilia. The orphan drug tranexamic acid (Cyclokapron) is for limited short-term use (2 to 8 days) in people with Hemophilia undergoing minor surgical procedures such as a tooth extraction. Cyclokapron reduces the need for blood transfusions after surgery. Genetically engineered Factor VIII became available for the treatment of Hemophilia after the Factor VIII derived from human blood was found to transmit viral illnesses such as AIDS and hepatitis. The new manufactured versions of Factor VIII are safer than the products used previously. In 1992 the FDA approved three biological products for treatment of Hemophilia B. Bebulin VH is manufactured by Osterreichisches Institute Fur Haemoderivate of Vienna, Austria. Bebulin VH is a Factor IX complex containing other clotting proteins. Mononine is a Factor IX product manufactured by Armour Pharmaceuticals. Alpha Nine is a Coagulation Factor IX (Human) manufactured by Alpha Therapeutic Corporation of Los Angeles, CA. Monoclonal Factor IX is a treatment for Hemophilia B. It is manufactured by Green Cross Inc. and Armour Pharmaceutical Company. Recombinant antihemophilic Factor is a treatment for hemorrhage in people with Hemophilia A. It is manufactured by Cutter Biological. Antihemophilic factor recombinant (Kogenate) treatment for bleeding or prophylaxis in patients with hemophilia has received approval from the FDA. Treatment is often necessary to prevent bleeding in patients or as a pre- treatment for persons who will be undergoing surgery. Genetic counseling will be of benefit for patients and their families. Therapies: Investigational The National Hemophilia Foundation provides research grants to scientists, and information to the public about hemophilia. Researchers at the National Institute of Diabetes, Digestive & Kidney Diseases have developed a method for growing skin cells (cultured endothelial cells) and a cell line that produces large amounts of Factor VIII:C. This is one of the clotting factors missing from the blood of people with Hemophilia A. People with Hemophilia frequently develop antibodies against Factor VIII:C obtained from blood donors. Large-scale production of endothelial-produced Factor VIII:C may provide an alternative to current therapies. The American Red Cross is developing coagulation Factor X as a treatment for Hemophilia. E(rGM-CSF) is a drug being tested for use in Hemophilia. The drug is manufactured by Schering Corp., 2000 Galloping Hill Rd., Kenilworth, NJ 07033. This experimental drug is being developed for other disorders, but its effects on the bone marrow has raised the possibility that it may have some benefit as a treatment for Hemophilia. Desmopressin Acetate (DDAVP high concentration (1.5 mg/ml) nasal spray) is being tested by Rorer Pharmaceutical Corp., Ft. Washington, PA, for treatment of Hemophilia A. This drug is marketed as a treatment for other disorders, but its possible use for Hemophilia is being investigated. Clinical trials are underway to study radiation synovectomy (removal of the synovial membrane in a joint) using 165-Dysprosium ferric hydroxide macroaggregate (165DY-FHMA). This is being investigated as a possible non- surgical approach for the treatment of inflammation in the knees of patients with hemophilia. Interested persons may wish to contact: Clement B. Sledge, M.D. Dept. of Orthopedic Surgery, Brigham and Women's Hospital 75 Francis St. Boston, MA 02115 (617) 732-5397 This disease entry is based upon medical information available through April 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Hemophilia, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 National Hemophilia Foundation 110 Green St., Suite 303 New York, NY 10012 (212) 563-0211 Coalition for Hemophilia B New England Medical Center 750 Washington St. Boston, MA 02111 (617) 956-5020 World Federation of Hemophilia Suite 1517 1155 Dorchester Boulevard West Montreal, Quebec H3B 2L3 Canada (514) 866-0442 Canadian Hemophilia Society, National Office 100 King St., West, Suite 210 Hamilton, Ontario L8P 1A2 Canada (416) 523-6414 The Haemophilia Society P.O. Box 9 16 Trinity Street London SE1 1DE England 01-407-1010 NIH/National Heart, Lung, and Blood Institute (NHLBI) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-4236 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. Pp. 1165. MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 1848-1865. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1104-1007. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 859-861. NASAL SPRAY DESMOPRESSIN (DDAVP) FOR MILD HEMOPHILIA A AND VON WILLEBRAND DISEASE, E.H. Rose et al.; Ann Intern Med (April 1, 1991, issue 114): Pp. 563-568.