$Unique_ID{BRK03476} $Pretitle{} $Title{Antithrombin III Deficiency, Congenital} $Subject{Antithrombin III Deficiency, Congenital AT III Deficiency Classical AT III Deficiency Variant Ia AT III Deficiency Variant Ib AT III Deficiency} $Volume{} $Log{} Copyright (C) 1986, 1987, 1990, 1992 National Organization for Rare Disorders, Inc. 99: Antithrombin III Deficiency, Congenital ** IMPORTANT ** It is possible that the main title of the article (Congenital Antithrombin III Deficiency) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms AT III Deficiency DISORDER SUBDIVISIONS: Classical AT III Deficiency Variant Ia AT III Deficiency Variant Ib AT III Deficiency 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. Antithrombin III (AT III), a blood protein, limits blood coagulation. Patients with a deficiency of AT III have a marked tendency to develop venous or arterial thrombosis, that is, blood clots blocking one of the blood vessels. The congenital deficiency is thought to occur in about one out of every 3000 to 5000 individuals. Symptoms The first episode of thrombosis usually occurs between the ages of 10 and 35 years. Often, surgery, pregnancy, delivery of a child, an accident, or oral contraceptives, (i.e., an event which increases the risk of thrombosis), precedes the episode. Women tend to develop thrombosis earlier than men because pregnancy and oral contraceptives are significant risk factors. Because a blood clot in an artery can cut off the blood supply to the tissue served by the blood vessel in which it occurs, tissue death may result from thrombosis. This is particularly dangerous when the brain, heart, or lungs are involved. Pulmonary embolism (i.e., the sudden blocking of an artery in the lung by a clot released from a leg vein), occurs in about 40% of individuals with hereditary AT III deficiency. Common sites of clot formation and occlusion include the veins deep in the legs and pelvic region, the more superficial veins in the legs, and the veins in the mesentery, a membrane supporting visceral organs. Clots in the veins of the legs and pelvis commonly produce swelling (or edema) of the involved extremity. Blood clots may also form in the heart in certain cardiac disorders and may result in thromboembolism to other organs such as the brain (producing stroke) or kidneys. Causes Congenital AT III deficiency is transmitted by an autosomal dominant gene. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.) Women may show signs of the disorder earlier than men. Two kinds of AT III deficiency have been recognized. In the classical form, the liver simply does not make enough AT III. In the variant forms, the liver makes both normal and abnormal AT III, and these may compete with each other in such a way that the normal protein is inhibited. The two forms of abnormal AT III are called variant Ia and variant Ib. Related Disorders AT III deficiency can be acquired. The risk of thromboembolism increases when AT III levels fall below 75% of normal amounts. This may occur when the coagulating system of the blood is active for sustained periods or on a large scale, after accidents or major surgery, for example. AT III may be lost in the urine when the kidneys fail to filter retained proteins in the blood, or it may be destroyed when proteins are broken down, in starvation for example. Other conditions which may cause an AT III deficiency include late pregnancy, birth control pills (estrogens), severe blood loss, and liver failure. Acquired AT III deficiency can usually be reversed. Therapies: Standard The goal in treatment of AT III deficiency is prevention of thrombosis. Preventive measures consist primarily of the use of oral anticoagulants, such as coumadin drugs, heparin and intravenous concentrated AT III. AT III replacement becomes particularly important when the risk of thrombosis is high; i.e., during pregnancy, surgery, etc. The protein should also be replaced when thrombosis has already occurred to help dissolve the clot. The amounts of heparin and AT III must be carefully monitored to prevent bleeding. Another side effect of treatment with AT III is an increased risk of developing hepatitis. Women prone to this disorder should not take oral contraceptives or other estrogenic medicines. Patients who exhibit any of the following should be screened for AT III deficiency: A family history of thrombosis Occurrence of thrombosis before age 35 Recurrence of thrombosis even with heparin therapy Deep vein thrombosis early in a woman's pregnancy Patients losing large amounts of protein in their urine. AT nativ has received FDA approval as standard treatment for Congenital Antithrombin III Deficiency. It is manufactured by Kabi Vitrum, Inc., 160 Industrial Dr., Franklin, CA 94505. The orphan drug Thrombate III, manufactured by Miles Labs, has received approval from the FDA and is now a standard therapy for the treatment of Antithrombin III Deficiency. The drug treats life-threatening blood clots. Therapies: Investigational The following pharmaceutical manufacturers are developing AT III for Congenital Antithrombin III Deficiency. commercial use in the United States: Cutter Laboratories 2200 Powell St. Box 8817 Emeryville, CA 94662 (415) 420-4000 Kabi Vitrum, Inc. 13111 Harbor Bay Parkway Alameda, CA 94501 (415) 769-4650 Hoechst-Roussel Pharmaceuticals, Inc. Route 202-206 North Somerville, NJ 08876 Clinical trials are being conducted on human Antithrombin III for use in preventing or arresting episodes of thrombosis in patients with congenital antithrombin III deficiency. Additionally, this drug is being tested for prevention of thrombosis in patients with antithrombin III deficiency who have undergone trauma, or who are about to undergo surgery or childbirth. For additional information on human antithrombin III, physicians can contact: The American National Red Cross National Headquarters 17th and E Streets, NW Washington, DC 20006 Antithrombin III may also be useful in the treatment of other coagulation disorders. For information on additional therapies that have been designated as Orphan Drugs in the last few months, please return to the main menu of NORD Services and access the Orphan Drug Database. This disease entry is based upon medical information available through March 1992. 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 Congenital Antithrombin III Deficiency, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 NIH/National Heart, Blood and Lung Institute Building 31, Room 8A-06 9000 Rockville Pike Bethesda, MD 20014 (301) 421-4236 American Liver Foundation 998 Pompton Avenue Cedar Grove, NJ 07009 (201) 857-2626 (800) 223-0179 The United Liver Foundation 11646 West Pico Blvd. Los Angeles, CA 90064 (213) 445-4204 or 445-4200 Children's Liver Foundation 14245 Ventura Blvd. Sherman Oaks, CA 91423 (818) 906-3021 References Substitution of AT III. Breddin, H.K., Kirchmaier, C.M. Wiener Klinische Wochenschrift 21 Dec 1984 (in english); 96(24):875-878. Antithrombin III deficiency and thromboembolism. Thaler, E., et al. Clinics in Haematology June 1981; 10(2):369-390.