DESMOPRESSIN SIDE EFFECTS AND THERAPY
CLINICAL
PRACTICE GUIDELINES
Hemophilia and von Willebrand’s Disease: 2. Management
(Edition 2, Update 2 [1999-07-07])
Desmopressin
Acetate
Desmopressin acetate (1-desamino-8-d-arginine vasopressin [DDAVP]),
a synthetic analog of the natural antidiuretic hormone, arginine
vasopressin, is capable of releasing von Willebrand factor into
the circulation from biosynthetic stores, thus increasing its
plasma level and that of Factor VIII. The intravenous administration
of 0.3 µg/kg (up to 20 #181;g in total) of desmopressin
causes a 2- to 10-fold (average 3- to 4-fold) rise in plasma levels
of Factor VIII and von Willebrand factor.<24-26> Following
desmopressin infusion, clotting-factor levels peak at 30 to 60
minutes and have a half-life similar to that of infused exogenous
clotting factors. Desmopressin can also be given subcutaneously
at the same dosage.<25,27> In Canada, in addition to the
usual formulation at 4 µg/mL desmopressin for intravenous
use, a formulation at 15 µg/mL suitable for both intravenous
and subcutaneous use is available. To limit the volume of subcutaneous
injection, a subcutaneous dose of 15 µg may be used in adults
if prior testing shows an adequate response. Intranasal preparations
(at 150 µg per spray [usual dose one spray in patients weighing
<50 kg or 2 sprays, one to each nostril, in patients weighing
>50 kg]) ideal for home care and especially useful for the
management of menorrhagia <27,28> can be obtained for individual
patients by "drop shipment" ordering arrangements with
Ferring. Desmopressin for intravenous or subcutaneous injections
currently costs about $10 (Cdn) for a 4 µg/mL vial and $35
for the 15 µg/mL vial. The intranasal preparation costs
about $386 each vial containing 25 sprays (150 µg per spray).
Therapeutic use
Desmopressin is the drug of choice for the treatment of patients
with mild hemophilia A (Factor VIII activity more than
5%) or
type 1, type 2A or 2N von Willebrand's disease whose response
to desmopressin has been found to be adequate in previous
testing.<24,26,29,30>
Overall, about 80% of patients with von Willebrand's disease will
respond to desmopressin. Patients with moderate to severe hemophilia
or type 3 von Willebrand's disease will not have an adequate response.
The administration of desmopressin to patients with type 2B <31>
or platelet-type (pseudo) von Willebrand's disease <32>
may be followed by platelet agglutination and, in most instances,
thrombocytopenia. Most hematologists would be reluctant to use
desmopressin in these patients, although evidence suggests that
desmopressin can be clinically efficacious <29,33,34>. Patients
with type 2B and platelet-type von Willebrand's disease can be
distinguished by their enhanced platelet aggregation response
to low-dose ristocetin (0.5 mg/mL).<31,32> This test
can be used to exclude these patients from desmopressin testing
and
therapy. Desmopressin is not effective in the treatment of
hemophilia B.
The response of Factor VIII and von Willebrand factor to
desmopressin falls, on average, to approximately 70% of the
original increment
without further decrease when repeated daily infusions are
administered
to patients.<35> Patients with von Willebrand's disease
tend to respond better to such repeated infusion than patients
with hemophilia, and are less likely to become unresponsive. During
major surgery or episodes of prolonged bleeding it may be necessary
to alternate desmopressin with supplemental coagulation products.
Patients with von Willebrand's disease tend to respond better
to such repeated infusion than patients with hemophilia, and are
less likely to become unresponsive. During major surgery or episodes
of prolonged bleeding it may be necessary to alternate desmopressin
with supplemental coagulation products. Desmopressin should not
be used in a major or life threatening hemorrhage where factor
VIII replacement is required.<36>
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