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$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
     [phone]

     Kabi Vitrum, Inc.
     13111 Harbor Bay Parkway
     Alameda, CA 94501
     [phone]

     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
     [phone]

     NIH/National Heart, Blood and Lung Institute
     Building 31, Room 8A-06
     9000 Rockville Pike
     Bethesda, MD  20014
     [phone]

     American Liver Foundation
     998 Pompton Avenue
     Cedar Grove, NJ  07009
     [phone]
     [phone]

     The United Liver Foundation
     11646 West Pico Blvd.
     Los Angeles, CA  90064
     [phone] or 445-4200

     Children's Liver Foundation
     14245 Ventura Blvd.
     Sherman Oaks, CA  91423
     [phone]

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.