MASAC Recommendations Regarding the Treatment of von Willebrand Disease
The following recommendations were approved by the Medical and
Scientific Advisory Council (MASAC) on February 23, 2001, and adopted by the
NHF Board of Directors on March 4, 2001.
von Willebrand disease is the most common inherited bleeding disorder. Recent
studies estimate the incidence at 1% to 2% of the general population. Since
it is inherited in an autosomal fashion, males and females are equally affected.
von Willebrand disease is associated with mucous membrane bleeding, excessive
bruising, and bleeding from cuts. It can result in excessive bleeding with
invasive dental work, during surgical procedures, and after accident or injury.
In women, excessive menstrual bleeding is often the major symptom.
Recently developed products have changed the treatment options for individuals
with von Willebrand disease. The following are current recommendations for
treating bleeding in these individuals.
1. Persons with type 1 von Willebrand disease should be treated with the synthetic
agent desmopressin (DDAVP Injectable or Stimate Nasal Spray for Bleeding, 1.5
mg/ml), and their response at first use should be documented for future reference.
For surgery, trauma, or other serious bleeding episodes, if hemostasis is not
achieved with DDAVP, a factor VIII concentrate rich in the high molecular weight
multimers of von Willebrand factor should be used (see #3 below).
2. Persons with type 2A, 2M, and 2N von Willebrand disease should be treated
with DDAVP if they have been shown by a DDAVP trial to be responsive.
with type 2B and type 3 von Willebrand disease, and those
with type 1, 2A, 2M, and 2N who have been shown to be nonresponsive
to DDAVP, should be treated with a factor VIII concentrate
that is known to contain the higher molecular weight multimers
of von Willebrand factor and that has been virally attenuated
to eliminate transmission of HIV and hepatitis A, B, and
C. Humate P (Aventis-Behring) has been approved by the FDA
for use in VWD. Two other products, AlphaNate (Alpha) and
Koate DVI (Bayer), may also be effective in these patients.
4. Because of the increased risk of HIV and hepatitis A, B, and C transmission,
cryoprecipitate should not be used except in an emergency situation where one
of the above-mentioned products is not available and delay of treatment would
be life- or limb-threatening.
5. Desmopressin is a potent antidiuretic agent, and fluid retention is a potential
complication of this drug. Both parenterally administered DDAVP and Stimate
Nasal Spray have been associated with the development of hyponatremia and seizures.
To minimize this risk, the following precautions should be observed when this
drug is used at home:
DDAVP and Stimate should be administered no more often than
once every 24 hours.
treatment for mucous membrane bleeding includes the antifibrinolytic
agent amino caproic acid (Amicar). This agent can be given orally
b. DDAVP and Stimate should be used for no more than three consecutive days
unless directed to do so by Hemophilia Treatment Center medical staff.
c. DDAVP and Stimate should not be used in children under the age of two years
or in pregnant women.
d. DDAVP and Stimate should be used with caution in the elderly and in individuals
with a history of heart disease, hypertension, or stroke.
e. If a patient is treated with DDAVP before surgery, the anesthesiologist
should be advised to avoid fluid overload and dilutional hyponatremia.
7. Prior to surgery in a patient with von Willebrand disease, consultation should
be obtained with a pediatric or adult hematologist who specializes in the management
of individuals with inherited bleeding disorders. This consultation should cover
such issues as the need for a DDAVP stimulation test; type of fluid replacement/fluid
restriction; dose and duration if DDAVP is to be used; appropriate dose, timing,
and duration of factor replacement therapy; and use of adjunctive medications
1. Mannucci PM. Desmopressin (DDAVP) for treatment of disorders of hemostasis. Prog
Hemost Thromb 1986; 8: 19-45.
2. Mannucci PM, Canciani MT, Rota L, Donovan BS. Response of factor VIII/von
Willebrand factor to DDAVP in healthy subjects and patients with haemophilia
A and von Willebrand disease. Br J Haematol 1981; 47: 283-93.
3. Mannucci PM, Lusher JM. Desmopressin and thrombosis. Lancet 1989; 2:
4. Nilsson IM, Hethagen S. Current status of DDAVP formulations and their use.
In Lusher JM, Kessler CM, eds. Hemophilia and von Willebrand disease in the 1990's. International
Congress Series/Excerpta Medica 1991; 943: 443-53.