A hereditary family of blood-clotting disorders caused
by a deficiency of the von Willebrand factor protein and factor VIII
protein, and characterized by prolonged bleeding.
Pseudohemophilia; Angiohemophilia; Constitutional
Thrombopathy; Minot-Von Willebrand Disease; Vascular Hemophilia;
Genetic, although a rare, acquired form exists.
Prevalence worldwide is estimated at 1%. Acquired
forms are much more rare.
Autosomal dominant or recessive inheritance
has been suggested as potential genetic transmission mode.
von Willebrand disease is the most common
inherited bleeding disorder in humans, and is secondary to abnormalities of
von Willebrand factor (vWF). There are several subtypes.
Mucocutaneous bleeding with normal platelet count,
elevated bleeding time, decreased ristocetin cofactor activity (ristocetin
is an antibiotic that alters normal vWF structure, causing platelet
aggregation), decreased vWF antigen (can be normal in type II), decreased
factor VIII activity; gel electrophoresis to determine vWF structure.
There are several subtypes. Type I has a partial
quantitative defect with normal structure, comprises 70% of cases, and
has mild to moderate bleeding; it is autosomal dominant. Type II has both
qualitative and quantitative defects. Type IIA (10% of cases) has mild to
moderate bleeding and a poor response to desmopressin acetate, while type IIB
(<5% of cases) has mild to moderate bleeding, thrombocytopenia, and a
contraindication to desmopressin acetate. Type IIM (reportable) has a variable
bleeding disorder with decreased vWF:Ag, vWF activity, and factor VII:C.
Type IIN (reportable and autosomal recessive) has a variable bleeding disorder that
may resemble hemophilia A. Type III (severe and rare, may be autosomal recessive)
has a complete deficiency of vWF. Acquired von Willebrand Disease is associated with myeloproliferative
disease, hypothyroidism, B-cell disorders, and cardiovascular defects,
resembles type 1 or 2, and has decreased plasma vWF antigen and normal
platelet vWF antigen.
Treatment: Desmopressin acetate, which increases the release of vWF, has a favorable
response in 80% of type I patients. The response in type II diseases is
variable, because an increased release of qualitatively poor vWF is not
useful for platelet binding. Desmopressin acetate may be contraindicated in
type IIB, because platelet aggregation may exacerbate thrombocytopenia, but
this is controversial. Estrogen may also increase production of vWF.
Replacement therapy, for failures or contraindications to desmopressin
acetate, was formerly with cryoprecipitate. However, virally inactivated
concentrates of factor VIII now exist, although the content of vWF varies.
The products of choice are Hemate-P and VHP vWF concentrate. Treatment is
empiric, although it should be continued for 7 to 10 days after major
surgical procedures, and for 3 to 5 days after minor ones; postpartum
hemorrhage may require 1 month of therapy. A suggested regimen for Hemate-P ...