von Willebrand Disease
An inherited bleeding disorder described by Finnish Physician
Erik Adolf von Willebrand
Low levels of a protein called von Willebrand
factor that helps the blood to clot
Von Willebrand disease is a condition when this
factor that doesn’t work properly .
Platelet Activation and
von Willebrand Factor (vWF)
In order for hemostasis to occur, platelets must
adhere to exposed collagen, release the contents
of their granules, and aggregate.
The adhesion of platelets to the collagen exposed
on endothelial cell surfaces is mediated by von
Willebrand factor (vWF).
Platelet Activation and
von Willebrand Factor (vWF)
The function of vWF is to act as a bridge between
a specific glycoprotein on the surface of platelets
(GPIb/IX) and collagen fibrils.
vWF binds to and stabilizes coagulation factor VIII.
Binding of factor VIII by vWF is required for
normal survival of factor VIII in the circulation.
von Willebrand Disease
Type 1
Low level of von Willebrand factor. The level of factor VIII may also
be lower than normal
Mildest and most common form of the disease.
About 3 out of 4 people diagnosed with vWD have type 1 disease.
Type 2
Defect in von Willebrand factor causes it to not work properly. Type
2 is divided into 2A, 2B, 2M, and 2N. Each is treated differently, so
knowing the exact type is important.
Type 3
No von Willebrand factor and very low factor VIII.
Type 3 is severe and very rare.
von Willebrand Disease - Type 2
Type 2A
the VWF multimers are not the right size. This stops the platelets
from making a good platelet plug.
Type 2B
the VWF multimers are not the right size and the VWF becomes too
active. It attaches to the platelets in the blood when it is not
supposed to. The body quickly gets rid of the platelets
Type 2M
the VWF is not able to stick to the platelets and a good platelet plug
does not form.
Type 2N
the VWF is not able to do its job as the carrier and protector
of factorVIII.
von Willebrand Disease
Incidence
roughly about 1 in 100 individuals.
Because most forms are rather mild, they are detected
more often in women, whose bleeding tendency
shows during menstruation.
It may be more severe or apparent in people with
blood type O.
von Willebrand Disease
Genetics
vWF gene is located on chromosome twelve
(12p13.2).
o Types 1 and 2 are inherited as autosomal dominant
traits and
o type 3 is inherited as autosomal recessive.
o Occasionally type 2 also inherits recessively.
von Willebrand Disease
Weibel-Palade bodies
Organelles in the endothelial cells
There are two major constituents
1. von Willebrand factor (vWF), a
multimeric protein involved in blood
coagulation
2. The second is P-selectin - binds to
passing immune cells (leukocytes).
von Willebrand Disease
Manifestations:
Bruising that's unusual in location or frequency
Abnormal menstrual bleeding
Bleeding in the mucous membranes
Excessive or prolonged bleeding after a tooth
extraction or tonsillectomy
Investigations
Bleeding time
Factor VIII level test (factor VIII coagulant)
von Willebrand factor antigen test (factor VIII antigen) - which
measures the amount of von Willebrand factor. ( mild if a person
has 20% to 40% of the normal, severe if the amount is less than 10% of
normal. )
Ristocetin co-factor activity test
measures how well the von Willebrand factor is working
von Willebrand factor multimers test - to classify the type of vWD
Platelet function tests
which determine how well the platelets work and help identify the type of vWD
or the presence of another disorder
Tests may need to be done more than once because these levels may rise
and fall over time in an individual.
Complications
Anemia.Women who experience heavy menstrual bleeding can
develop iron deficiency anemia.
Swelling and pain. If abnormal bleeding occurs in the joints or
soft tissue, swelling and severe pain can result.
Death from bleeding. Rarely, someone with von Willebrand
disease may experience uncontrolled bleeding that can be life-
threatening and needs emergency medical attention.
von Willebrand Disease
Treatment:
Human derived medium purity factor VIII
concentrates complexed to vWF
Mild cases - treated with desmopressin (1-desamino-8-
D-arginine vasopressin, DDAVP)
Rises patient's own plasma levels of vWF by inducing
release of vWF stored in the Weibel-Palade bodies in the
endothelial cells
Replacement therapies:
infusions of prepared doses of concentrated blood-
clotting factors containing von Willebrand factor and
factor VIII (Humate-P, others)
von Willebrand Disease
Treatment:
Contraceptives. For women, these can be useful for controlling
heavy bleeding during menstrual periods. The estrogen hormones
present in birth control pills can boost levels of von Willebrand
factor and factor VIII activity.
Clot-stabilizing medications. These anti-fibrinolytic
medications — such as aminocaproic acid and tranexamic acid —
can help stop bleeding by slowing the breakdown of blood clots,
esp before or after a surgical procedure or tooth extraction.
Drugs applied to cuts. A fibrin sealant (Tisseel VHSD) placed
directly on a cut helps curtail bleeding. These substances are
applied like a glue using syringes.
