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$Unique_ID{BRK04318}
$Pretitle{}
$Title{Von Willebrand Disease}
$Subject{Von Willebrand Disease Angiohemophilia Vascular Hemophilia Minot-Von
Willebrand Disease Pseudohemophilia Constitutional Thrombopathy
Willebrand-Juergens Disease Hemophilia }
$Volume{}
$Log{}

Copyright (C) 1987, 1988, 1990, 1991, 1992 National Organization for Rare
Disorders, Inc.

375:
Von Willebrand Disease

** IMPORTANT **
It is possible the main title of the article (Von Willebrand Disease) is
not the name you expected.  Please check the SYNONYMS listing on the next
page to find alternate names, disorder subdivisions, and related disorders
covered by this article.

Synonyms

     Angiohemophilia
     Vascular Hemophilia
     Minot-Von Willebrand Disease
     Pseudohemophilia
     Constitutional Thrombopathy
     Willebrand-Juergens Disease

Information on the following disease can be found in the Related
Disorders section of this report:

     Hemophilia

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.


Von Willebrand Disease is a hereditary blood clotting disorder
characterized by prolonged bleeding.  Blood clotting is slowed due to a
deficiency of the Von Willebrand factor protein and factor VIII protein (the
factor VIII complex).  Also, platelets do not stick normally causing
excessively slow clotting time.  Increased risk of excessive bleeding
following surgery, dental procedures or injury occurs in patients with this
disorder.  With proper treatment and appropriate precautions, few patients
become seriously handicapped by Von Willebrand Disease.  The tendency to
prolonged bleeding usually decreases with age.

Symptoms

Patients with Von Willebrand Disease tend to experience prolonged bleeding,
usually of the gastrointestinal tract or nosebleeds (epistaxis).  People with
this disorder tend to bruise easily and bleed excessively following injuries,
surgery, menstruation and/or childbirth.  Very rarely, internal bleeding into
joints may also occur.

Causes

Von Willebrand Disease is usually inherited as a dominant trait.  Decreased
production of the Von Willebrand factor protein and blood factor VIII (the
factor VIII complex), combined with a blood platelet abnormality does not
allow the blood to coagulate properly, causing excessive bleeding.  A severe
form of Von Willebrand Disease has recently been identified; this type of the
disorder can be inherited as either a recessive or a dominant trait.

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 recessive disorders, the condition does not appear unless a person
inherits the same defective gene from each parent.  If one receives one
normal gene and one gene for the disease, the person will be a carrier for
the disease, but usually will show no symptoms.  The risk of transmitting the
disease to the children of a couple, both of whom are carriers for a
recessive disorder, is twenty-five percent.  Fifty percent of their children
will be carriers, but healthy as described above.  Twenty-five percent of
their children will receive both normal genes, one from each parent and will
be genetically normal.

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.

A disorder similar to Von Willebrand Disease which may be acquired during
later adult life has also been recently identified.  This disorder is caused
by over-production of an antibody that destroys the Von Willebrand factor
protein.  Von Willebrand Disease can also be acquired in association with
other diseases including certain kidney diseases, a type of Leukemia, or
congenital heart disease involving an abnormal heart valve.

Von Willebrand Disease differs from the better known bleeding disorder
Hemophilia because it affects both sexes.  Persons with Hemophilia have
deficiencies of the factor VIII protein with normal amounts of the Von
Willebrand factor protein.  No platelet abnormality is found in Hemophilia
patients.

Affected Population

Von Willebrand Disease usually begins in infancy or early childhood.  This
disorder seems to affect females more than males, although both can be
affected.  Some forms can be acquired during adulthood due to non-genetic
causes.

Related Disorders

Hemophilia is a blood clotting disorder inherited as an X-linked recessive
trait.  Symptoms are caused by deficiencies of blood clotting factor VIII
protein.  Hemophilia affects males exclusively and the degree of severity is
determined by the percentage of normal active clotting factor in the blood.
Persons with severe hemophilia usually have less than 1% of the normal levels
of active clotting factor present in their blood.  The general term
"Hemophilia" includes Hemophilia A (Classical Hemophilia, Factor VIII
deficiency), and Hemophilia B (Christmas Disease, Factor IX deficiency).
(For more information on this disorder, choose "hemophilia" as your search
term in the Rare Disease Database.)

Hemophilia and Von Willebrand Disease are inherited through different
modes of transmission; Hemophilia is caused by an x-linked recessive gene
whereas Von Willebrand is usually caused by one dominant gene.

Other rare blood clotting disorders may have similar symptoms but may not
be classified as types of hemophilia due to different modes of inheritance,
transmission and different blood clotting factors involved.

Therapies:  Standard

Patients with Von Willebrand Disease should take special precautions before
any surgical procedure, after an accident or unexplained bleeding.  Blood or
blood plasma transfusions before surgery or childbirth can reduce the risk of
hemorrhage.  Transfusions of intravenous (frozen or stored) blood plasma can
elevate factor VIII protein and the Von Willebrand factor protein thus
allowing blood to clot properly.  Transfusions of whole blood can also raise
the level of these factors and improve clotting ability.

Some patients with mild cases of Von Willebrand Disease have undergone
surgical procedures with daily dosages of the drug Desmopressin Acetate
(DDAVP).  This is a synthetic agent which can be used as a substitute for
blood products.  It can stimulate the release of the factor VIII complex
molecules from cells lining blood vessels thereby shortening clotting time.
In some cases, additional treatment with cryoprecipitates (frozen blood
products) may be required to control excess bleeding.  Careful monitoring of
dosages is recommended to avoid other complications.

An injectable form of DDAVP, an antidiuretic peptide, is manufactured by
Rorer Pharmaceutical, Corp., Ft. Washington, PA.

Cryoprecipitates (frozen blood products) remain the best way to replace
the factor VIII complex especially in severe cases of Von Willebrand Disease.
Careful medical supervision of dosages is also necessary with this treatment.

The antifibrinolytic drug, aminocaproic acid (amicar) can aid in reducing
bleeding.

Individuals with Von Willebrand Disease should wear some type of
identification such as the Medic-Alert bracelet.  Emergency information
should include directions to treat bleeding with Desmopressin Acetate (DDAVP)
or cryoprecipitates.

People affected by this disorder should avoid aspirin and drugs that
prolong bleeding.  Activities that are likely to be associated with injuries
should be avoided.  Genetic counseling can be helpful to families and
patients.

Therapies:  Investigational

The FDA has approved the following orphan drug for testing as treatment for
Von Willebrand patients:

     Antihemophilic Factor, Human (Humate P)
     Manufactured by:
     Behringwerke Aktiengesellschaft
     500 Arcola Rd.
     P.O. Box 1200
     Collegeville, PA  19426-0107

A form of Desmopressin Acetate (DDAVP) administered through the nose
(intranasally) is being studied as a possible treatment for Von Willebrand
Disease.

The Food and Drug Administration (FDA) has awarded a research grant to
Marjorie Read, Ph.D., University of North Carolina, Chapel Hill, NC, for
studies on coagglutinin as a treatment for von Willebrand Disease.  The
orphan drug was approved for testing by the FDA and is manufactured by Rorer
Pharmaceutical Corp., Ft. Washington, PA.

The FDA has approved the following drug for testing as treatment for Von
Willebrand Disease patients:

The orphan drug NovoSeven (factor VIIa) (recombinant DNA origin)) is
being tested for treatment of patients without antibodies against factor
VIII/IX by Novo-Nordisk A/S, Copenhagen, Denmark.

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
November 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 Von Willebrand Disease, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     NIH/National Heart, Lung and Blood Institute
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

Although Von Willebrand Disease is not a form of Hemophilia, National
Health Agencies providing information, referrals and support groups for Von
Willebrand Disease are organizations that are primarily concerned with
Hemophilia:

     National Hemophilia Foundation
     19 W. 34th Street
     New York, NY  10001
     [phone]
     (Supplies lists of Hemophilia centers throughout the country).

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

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

     The Haemophilia Society
     P.O. Box 9
     16 Trinity Street
     London SE1 1DE
     England
     01-407-1010

For more information on genetics and genetic counseling referrals, please
contact:

     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

A HUMAN MYELOMA-PRODUCED MONOCLONAL PROTEIN DIRECTED AGAINST THE ACTIVE
SUBPOPULATION OF VON WILLEBRAND FACTOR:  E.G. Bovill, et al.; Am J Clin
Pathol (Jan. 1986, issue 85(1)).  Pp. 115-123.

VON WILLEBRAND'S DISEASE AND PREGNANCY:  MANAGEMENT DURING DELIVERY AND
OUTCOME OF OFFSPRING:  J.R. Chediak, et. al.; Am J Obstet Gynecol (Sept.
1986, issue 155(3)).  Pp. 618-624.

VON WILLEBRAND SYNDROME:  I. Scharrer; Behring Inst Mitt (Feb. 1986,
issue 79).  Pp. 12-23.

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.