vonWillebrand Factor (VWF) is actually a series of multimeric plasma glycoproteins
with molecular weight ranging from 40,000 to 20 million.
VWF serves two main functions:
It facilitates platelet adhesion to the vessel wall by linking platelet
membrane receptors to the subendothelium.
It serves as the plasma carrier for Factor VIII and actually stabilizes
the molecule. The half-life of Factor VIII is approximately 8 minutes
in the absence of VWF and 8 hours in the presence of VWF.
VWF is synthesized in endothelial cells and megakaryocytes.
II. vonWillebrand Disease
vonWillebrand Disease (VWD) is the most common inherited bleeding disorder,
with an estimated incidence as high as 1 in 100 to 1000.
Classification: There are three main types of VWD.
1. Type I - by far the most common form. Inheritance is
autosomal dominant. Most patients are heterozygotes.
Mild to moderate decrease in plasma VWF concentrations.
Most patients have mild disease with excessive bleeding after surgery or
trauma.
2. Type II - Rare, patients have normal levels but dysfunctional
VWF, leading to decreased VWF activity.
IIa - deficiency in high and medium molecular weight VWF due to either
inability to secrete them from the megakaryocyte or endothelial cell or
due to proteolysis as soon as they enter the circulation.
IIb - also a deficiency in high molecular weight VWF, but due to inappropriate
binding of VWF to platelets. This leads to platelet aggregation and
eventual clearing of the aggregates from the circulation.
3. Type III - Inheritance is autosomal recessive. Most
individuals are the offspring of two Type I patients and therefore homozygous.
(the patients initially described by von Willebrand)
They may inherit a different abnormality from each parent, leading to a
double heterozygote.
These individuals have zero VWF levels and no detectable activity, leading
to diminished platelet aggegration and therefore mucosal bleeds.
This also leads to profound deficiencies in Factor VIII levels, causing
hemarthroses and bleeding into potential spaces as in hemophilia.
Laboratory Evaluation: comparison between Type I and Type III.
Type II not included because of its rarity.
Type I
Type III
Factor VIII antigen (aka VWF)
40-60%
0%
Factor VIII activity
40-60%
2-3%
Ristocetin cofactor assay (VWF activity)
decreased
decreased
PTT / Bleeding time
normal / prolonged
prolonged / prolonged
Options for therapy:
1. Cryoprecipitate (which is rich in VWF) or Factor VIII concentrates
(which contain some high molecular weight VWF)
For minor bleeding such as epistaxis, a single dose may suffice.
Perioperatively, either must be given twice a day until 48 - 72 hours
post-op
2. DDAVP
Triples the plasma VWF in normal patients and in those with mild VWD.
Not effective in Type III, because there is no VWF to begin with. (3x0=0)
Should do trial to ensure that patient will respond before actually using
DDAVP for treatment.
Effects last 2-3 days before tachyphylaxis can occur/
3. Note: Aspirin is totally contraindicated in
patients with VWD because of inhibitory effect on platelet aggegration.
This would exacerbate VWD.
There is an acquired form of VWD, which occurs when antibodies inhibit
VWF or when tumors (such as lymphoid tumors) that adsorb VWF on to
their surface are present.
