Type 1: Autosomal-dominant pattern of inheritance with reduced penetrance

• Penetrance is how often a gene is expressed when it is present, so reduced penetrance means that people could have the mutated gene but have a decreased chance of expressing it

• Since the dominant gene is not always expressed when a person has it, a family pedigree could manifest in a recessive pattern. The trait may not be present in every generation.

• Since VWD is an autosomal-dominant trait, there is no carrier status

• Interestingly, a person with type O blood type are more likely to express the gene

Type 2: Autosomal-dominant pattern of inheritance

• This mode of inheritance ensures that everyone who has the mutated gene will express its phenotype.

• On a family pedigree, the trait will be present in all generations

• A person heterozygous for the trait will pass it along to their children 50% of the time while a person homozygous for the trait will pass it along to their children 100% of the time

Type 3: Autosomal-recessive pattern of inheritance

• In order to express the trait for VWF, a person needs to be homozygous for the trait

• On a family pedigree, the trait is not present in all generations and may skip generations.

• There is a carrier status and a person that is a carrier can pass along the gene to their children even if they do not express the phenotype

*Acquired von Willebrand disorder (AVWD): Very rare, but sometimes the body can destroy its own VWF secondary to disease process such as Lupus or Multiple Myeloma (Tiede et al., 2011). This cannot be inherited by children.

Type 1:

• The most common, causing mild to moderate bleeding

• Reduced amount of circulating VWF available in body

Type 2:

• Second most common form, causing mild to moderate bleeding

• VWF is defective and not operating correctly

• Very difficult to diagnose because levels of VWF are normal and do no indicate an impairment

Type 3:

• Rarest form, causes severe, sometimes life threatening bleeding

• Extremely low VWF

This involves discussing patient history of easy or heavy bleeding as well as discussing family history of bleeding disorders

2. Laboratory testing

Lab screenings can be completed to assess blood clotting ability, clotting times, and anemia (CDC, 2024). These labs include:

• Activated partial thromboplastin time (APTT) test

• Prothrombin time (PT) test

• Fibrinogen test

• Complete Blood Count (CBC)

There is not a single lab test to diagnose VWD but a series of labs are done and carefully correlated with each other to determine which type. According to Roberts and Flood (2015), labs that can help assess quantity and quality of VWF include:

• VWF antigen

• VWF ristocetin cofactor activity

• Factor VIII activity

• VWF multimer distribution

• VWF collagen binding

• VWF–platelet binding

• Low-dose ristocetin-induced platelet aggregation

• VWF-FVIII binding

• VWF propeptide

• VWF gene sequencing

According to Laffan et al. (2021), treatments for VWD are often only needed for management of bleeding episodes or for bleeding prophylaxis, treatments include:

1. Tranexamic acid: inhibits fibrinolysis, making it helpful to use in conjunction with mild procedures or bleeding episodes to prevent bleeding

2. Desmopressin: activates platelets and increases the release of functioning VWF and factor VIII from endothelial cells. Useful in treatment of type 1 VWD. Response of medication decreases with frequent use.

3. VWF concentrate: VWF replacement to increase levels of the deficient VWF.

4. Iron or blood transfusions: treat anemia from blood loss/menstrual cycles

An article by Janbain and Kouides (2022) discusses management of VWD and pregnancy.

• Women with type 1 can have an increase in VWF and improvements in symptoms

• Women with type 2 can also have an increase in VWF but as they are defective, it is not as beneficial

• Women with type 3 do not typically have an increase in VWF and remain low throughout their pregnancy.

• Although levels of VWF can increase during pregnancy, VWD still poses concerns for pregnancy women. In fact, there is "a 5-40% prevalence of PPH [post-partum hemorrhage] compared to the 2-10% prevalence in the general population" (p. 1309).

• Pregnant women need lab monitoring during pregnancy, if factor levels decrease to less than 50%, possible factor replacement is needed. If factor replacement is initiated, levels must be closely monitored to prevent thrombosis (Janbain & Kouides, 2022).

Beery, T. A., Workman, L. M., & Eggert, J. A. (2018). Genetics and genomics in nursing and health care. F.A. Davis Company.

Centers for Disease Control and Prevention. (2024, May 15). About von Willebrand disease. Centers for Disease Control and Prevention. https://www.cdc.gov/von-willebrand/about/index.html

COR2ED The Heart of Medical Education. (2022). When to consider von Willebrand disease. YouTube. https://www.youtube.com/watch?v=z4U0GKKrUOk&t=1s

Janbain, M., & Kouides, P. (2022). Managing Pregnant Women with Hemophilia and von Willebrand Disease: How Do We Provide Optimum Care and Prevent Complications? International Journal of Women’s Health, 14, 1307–1313. https://doi.org/10.2147/IJWH.S273043

Laffan, M., Sathar, J., & Johnsen, J. M. (2021). von Willebrand disease: Diagnosis and treatment, treatment of women, and genomic approach to diagnosis. Haemophilia : The Official Journal of the World Federation of Hemophilia, 27(S3), 66–74. https://doi.org/10.1111/hae.14050

Roberts, J. C., & Flood, V. H. (2015). Laboratory diagnosis of von Willebrand disease. International journal of laboratory hematology, 37 Suppl 1(Suppl 1), 11–17. https://doi.org/10.1111/ijlh.12345

Svensson, P. J., Bergqvist, P. B. F., Juul, K. V., & Berntorp, E. (2014). Desmopressin in treatment of haematological disorders and in prevention of surgical bleeding. Blood Reviews, 28(3), 95–102. https://doi.org/10.1016/j.blre.2014.03.001

Takayama, W., Endo, A., Koguchi, H., Sugimoto, M., Murata, K., & Otomo, Y. (2018). The impact of blood type O on mortality of severe trauma patients: a retrospective observational study. Critical Care (London, England), 22(1), 100–100. https://doi.org/10.1186/s13054-018-2022-0

Tiede, A., Rand, J., Budde, U., Ganser, A., & Federici, A. (2011, June 23). How I treat the acquired von Willebrand syndrome . American Society of Hematology. https://ashpublications.org/blood/article/117/25/6777/24352/How-I-treat-the-acquired-von-Willebrand-syndrome

Photos

Von Willebrand Disease Blood Transfusion - Search Images

dominant vs recessive traits - Search Images

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Annual Global Survey

desmopressin - Search

Blood Types Explained - A, B, AB and O | Red Cross Blood Services

vWD - Search Images

VWD infusion - Search Images

• Is an antidiurecic hormone

• Increases the levels of VWF and Factor VIII 2-6 times by stimulating the extrarenal arginine vasopressin (AVP) V2-receptors in endothelial cells.

• Hemostatic benefits aid those with hemophilia A, VWD, uremia, liver cirrhosis, and congenital or acquired platelet dysfunction

• Can be administered subcutaneously, intravenously, and intranasally

• Side effect include hyponatremia secondary to anti-diuretic effect with repeated doses

• Used preventatively, before surgeries or procedures and also to treat acute bleeding