Von Willebrand's disease

Von Willebrand disease (VWD) is primarily an inherited blood clotting disorder that results from a quantitative deficit or qualitative dysfunction of the blood coagulation protein von Willebrand factor (VFW).  About 1% of the U.S. population has some form of VWD. It occurs equally among men and women, but women more frequently experience excessive bleeding because of menstruation and after childbirth (CDC 2021).

Quantitative deficiency -  Mutations in the VWF gene on chromosome 12 can cause more rapid clearance of VWF from the circulation or decreased endothelial biosynthesis and secretion of VWF.

• Type 1 VWD - About 85% of people treated for VWD have Type 1, in which a person has lower-than-normal  blood levels of VWF.  Persons with Type 1 VWD may also have low levels of factor VIII (8), another type of blood-clotting protein.
• Type 3 VWD - Only 3% of people with VWD have Type 3.  This is the most severe form of VWD, in which a person has very little or no VWF and low levels of factor VIII.

Qualitative dysfunction (Type 2) - With this type of VWD, although the body makes normal amounts of the VWF, the factor does not work the way it should. Type 2 is further broken down into four subtypes―2A, 2B, 2M, and 2N.

• Type 2A, the VWF molecule is not the right size and doesn’t help the platelets attach together in order to form a clot.
• Type 2B, the VWF attaches to platelets at the wrong time (when there is no injury). The body removes the platelets attached to VWF, causing a reduced amount of both platelets and VWF in the blood when needed to form a clot.
• Type 2M, the VWF does not attach to the platelets as it should, which decreases the platelets’ ability to form a clot when an injury occurs.
• Type 2N, the VWF attaches to the platelets normally. However, the VWF does not attach to another protein, Factor VIII (8), which is also needed for blood to clot. This causes the body to remove the Factor VIII (8) protein.
  

Inheritance pattern

There are two different ways that VWD can be inherited, autosomal dominant or autosomal recessive, depending on the type of VWD present.  An autosomal dominant "inherited" disorder, means only one copy of abnormal gene can result in disease. The most severe form of the condition is "autosomal recessive," which requires both of your parents to pass an abnormal an gene (CDC 2021).

Acquired VWD (AvWD)

AvWD has been associated with conditions that deplete VWF, including:

• Hypothyroidism can result in decreased synthesis of factor VIII and von Willebrand factor (VWF)
• Thrombocythaemia of various myeloproliferative disorders may present with von Willebrand factor antigen (VWF: Ag).
• Systemic lupus erythematosus
• VWF antibody bound to VWf/Vlll increases clearance
• Drug-induced AVWS has been described in association with the use of pesticides valproic acid, ciprofloxacin, griseofulvin, tetracycline, thrombolytic agents and hydroxyethyl starch (Michiels 2001).

Reference

CDC (2021). What is von willebrand disease? https://www.cdc.gov/ncbddd/vwd/facts.html.

CDC (2021). How von Willebrand Disease Is Inherited. https://www.cdc.gov/ncbddd/vwd/inherited.html

Michiels JJ, Budde U, van der Planken M, van Vliet HH, Schroyens W, Berneman Z. (2001). Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. Best Pract Res Clin Haematol. https://pubmed.ncbi.nlm.nih.gov/11686107/