A newborn boy was experiencing nosebleeds, blood in his urine, and easy bruising. Initial tests were normal except for slightly viscous blood. A doctor suspected von Willebrand disease (VWD) and tested for the von Willebrand factor (VWF). The VWF test was negative, indicating a defect in the VWF protein. VWD is caused by defects in the VWF protein, which is important for platelet binding and clotting. It affects up to 1% of the population and treatment involves drugs like desmopressin to stimulate VWF release.

1. CASE STUDY
Von Willebrand’s Disease
By: Austin Fridrich

2. THIS IS THE PATIENT YOU ARE PRESENTED WITH:
• A little baby boy in the birthing center was just born 2 days ago in the hospital. The
child has only been showing a few symptoms, but they seem to be quite serious.
• The little boy has been having nosebleeds that can not seem to be stopped, there is
blood in his urine, and the child is bruising much to easily for the good care he has
been receiving from the nurses.
• Another week goes by and the child still is having the same issues, without showing
signs of improvement.

3. WHAT IS YOUR INITIAL DIAGNOSIS GOING TO BE?
WHAT TEST ARE YOU GOING TO PERFORM?
• The child is clearly experiencing some sort of internal disorder, and is most likely related to
something within the child’s blood.
• An ultrasound is ordered to determine if there is any sign of internal damage
• It comes back clear
• This is a clear sign that blood test should be ordered for multiple different tests, some of them
being:
• CBC (complete blood count) – tests white and red blood cell counts, platelet count, hematocrit, and brain
neurotic peptide.
• Multiple blood coagulation tests – PT (prothrombin time), PTT (partial thromboplastin time), and INR
(international normalized ratio).
• The results for all tests are fairly normal, except for the blood being slightly more viscous than it should

4. A POSSIBLE SOLUTION:
• Finally, one doctor on the team assigned to the child thinks he may know what it is and
suggest ordering a VWF test
• VWF ( Von Willebrand Factor) – a clotting protein, that is responsible for binding to factor
VIII, and binding to platelets in blood vessel walls that create a clot during the clotting process
• Factor VIII – another key clotting protein
• Results:
• The VWF test comes back negative
• The negative result means that this child is either missing or maintain a defective Von
Willebrand protein factor

5. VON WILLEBRAND DISEASE (VWD)
• Von Willebrand disease is caused by the missing biomolecule VWF protein
• Without this VW protein, factor VIII can not clot, as well as the platelets within the
blood vessels losing their ability to form clots effectively
• VWD is actually the most common bleeding disorder, as it affects up to 1% of the
U.S. population
• However, it is often unheard since it is almost always diagnosed shortly after birth,
since it can be determined by a simple coagulation blood test

6. SYMPTOMS AND TYPES OF VON WILLEBRAND’S
• Symptoms: frequent nosebleeds, easy bruising, excessive bleeding after injury or
invasive operations
• In women VWD causes a longer lasting menstrual cycle, menorrhagia, and hemorrhaging
after child birth
• Types:
• 1(60-80% of cases) – the patient has 20-50% of VWF protein, usually mild symptoms
• 2 (15-30%) – this is a qualitative type as in it is diagnosed off of how the patients
symptoms present themselves, usually still mild to moderate symptoms
• 3 (5-10%) – the most severe case, occurring when the patient has almost no VWF clotting
protein
• This can include spontaneous bleeding episodes that often leads into their joints and muscles

7. THE MOLECULE
• Genetics
• VWD is an inherited disorder in almost all type 1 and 2 cases
• It is inherited in an autosomal dominant pattern and carried on chromosome 12
• Meaning 1 copy of the affected gene in each cell is enough to cause the disease
• In type 3 cases the disorder is inherited again, but it a different pattern
• The inheritance pattern now becomes autosomal recessive (still chromosome 12)
• This means that both copies of the gene in each cell now have that mutation
• This autosomal recessive inheritance is also thought to be part of the reason for why type 3 is more
severe than types 1 and 2

8. THE VWF PROTEIN MECHANISM
• How does VWF work in a healthy body?
• Lets say you get a cut. Once, this happens our body wants to immediately repair, and so
VWF protein will assist with that by forming a hemostatic plug
• VWF travels down your blood vessel in a globular shape, and when it arrives at the site of
repair it uncoils itself

9. HOW DOES VWF PROTEIN BIND TO THE
BLOOD VESSEL WALLAND THE PLATELETS?
• Unwinding at the repair site by VWF will unveil A1 domains and A3 domains
• A1 domains are actually the platelet receptors and will “catch” them as they move
through in the blood (initiation of clotting process)
• A3 domains are collagen binding sites; therefore, when uncoiled the A3 domains of VWF
will attach/anchor to the collagen fibers of the blood vessel wall
• In order to form the entire clot successfully; after the first layer of platelets forms on
top of the VWF strand, a new VWF protein will come by and mount itself to the top
of the platelets, this continues until VWF strands have extended far enough across
the blood vessel to stop the bleeding

10. TREATMENT FOR THOSE WITH VWD
• Dependent on the type and severity of the disease
• The most common treatment however is DDVAP (desmopressin acetate)
• It is a synthetic version of our bodies natural response to vasopressin
• Also, DDVAP will stimulate the release of VWF protein, from what amount there is
dependent on that person’s condition
• The DDVAP treatment is easy to administer as it is either an injection or a nasal
spray most of the time

11. REFERENCES
• https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-
Disorders/Von-Willebrand-Disease
• https://ghr.nlm.nih.gov/condition/von-willebrand-disease#genes
• http://www.humate-p.com/Professional/About-Humate-P/Mechanism-of-
Action.aspx