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$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
     [phone]

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
     [phone]

     National Hemophilia Foundation
     110 Green St., Suite 303
     New York, NY  10012
     [phone]

     Coalition for Hemophilia B
     New England Medical Center
     750 Washington St.
     Boston, MA  02111
     [phone]

     World Federation of Hemophilia
     Suite 1517
     1155 Dorchester Boulevard West
     Montreal, Quebec H3B 2L3
     Canada
     [phone]

     Canadian Hemophilia Society, National Office
     100 King St., West, Suite 210
     Hamilton, Ontario L8P 1A2
     Canada
     [phone]

     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
     [phone]

For Genetic Information and Genetic Counseling Referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY 10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

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.