About
Von Willebrand Disease
Von Willebrand Disease (VWD) is the most common genetic blood disorder that impairs effective blood clotting in response to injury [1]. The disease is caused by the dysfunction of a protein known as the Von Willebrand Factor (VWF), which plays a large role in the formation and recruitment of blood clots [1]. At the site of injury, the blood vessel will respond to bleeding by triggering a number of proteins in the blood to form clots. The proteins in this signaling cascade act together to stop excess bleeding and initiate a vessel healing process. Among these proteins is the VWF protein, which is necessary for the adhesion of clotting components that bind together in a blood-plug formation. Individuals with VWD will experience a higher incidence of bleeding when injured, as the VWF is either non-functioning, improperly functioning, or functioning at harmfully low levels. The disease may result in a delay in the stop of bleeding as well as heavy bleeding. More severe consequences can cause defects in organ function and even fatality [1].
Causes and Inheritance
Figure 1: Haemophilia Foundation Australia. [6]
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Inheritance:
Von Willebrand Disease (VWD) is an Autosomal Dominant Disease. This means that if one parent has a genetic component that causes VWD, there is a 50% chance of having a child with VWD [2]. Prevalence: VWD is the most common blood order and effects up to 1% of the U.S. population [3]. |
Causes of Developing VWD:
Mutations in the VWF gene that encode for the VWF protein can effect the quality and quantity of VWF protein that is produced. The decreased levels of VWF protein is the most common form of VWD [4]. These mutations are almost always inherited, although it is possible (and rare) for spontaneous mutations to occur in the VWF gene that can result in the development of VWD.
Mutations in the VWF gene that encode for the VWF protein can effect the quality and quantity of VWF protein that is produced. The decreased levels of VWF protein is the most common form of VWD [4]. These mutations are almost always inherited, although it is possible (and rare) for spontaneous mutations to occur in the VWF gene that can result in the development of VWD.
Age of symptom onset for Von Willebrand Disease can vary, as can severity. Most commonly, individuals with the disease experience [4]:
Treatments for Von Willebrand Disease will depend on the type a patient is diagnosed with. The three main types of VWD are as follows: Type 1, Type 2, and Type 3 [4]. Type 1 is the mildest form of the disease and generally the most common. It is the result of lower than normal levels of Von Willebrand Factor protein in the blood, and will typically only cause an issue in response to surgery or injury. Type 2 is in patients whose Von Willebrand Factor protein functions improperly, and cannot efficiently aid blood clot formation as needed. Patients with Type 2 VWD will experience more frequent and heavier bleeding. Type 3 is the most severe form of VWD, and this occurs when their is very low levels of VWF protein, sometimes none at all, and uncontrollable bleeding is common. Heavy bleeding in joints and muscle following injury may occur, and traumatic injuries may be immediately life threatening for these patients [4].
Treatments by Type of VWD:
Type 1: Desmopressin Acetate Injection is often used to treat mild forms of VWD. This involves injection of Desmopressin Acetate into the vein of patients to trigger the release of VWF proteins into the blood and increase levels of VWF. Desmopressin Acetate Nasal Spray is also available to be used for the same effect [3].
Type 2 and Type 3: Factor Replacement Therapy is used for more severe forms of VWD and involves the use of recombinant VWF as well as medicines with high levels of VWF. These treatments are administered via injection in the vein in the arm [3].
- Large and frequent bruising on the skin
- uncontrollable and long-lasting nosebleeds
- heavy and long-lasting bleeding when cut or injured
- heavy and prolonged bleeding after surgery or even losing/removing teeth
- women may experience very heavy menstruation or bleeding after labor [4]
Treatments for Von Willebrand Disease will depend on the type a patient is diagnosed with. The three main types of VWD are as follows: Type 1, Type 2, and Type 3 [4]. Type 1 is the mildest form of the disease and generally the most common. It is the result of lower than normal levels of Von Willebrand Factor protein in the blood, and will typically only cause an issue in response to surgery or injury. Type 2 is in patients whose Von Willebrand Factor protein functions improperly, and cannot efficiently aid blood clot formation as needed. Patients with Type 2 VWD will experience more frequent and heavier bleeding. Type 3 is the most severe form of VWD, and this occurs when their is very low levels of VWF protein, sometimes none at all, and uncontrollable bleeding is common. Heavy bleeding in joints and muscle following injury may occur, and traumatic injuries may be immediately life threatening for these patients [4].
Treatments by Type of VWD:
Type 1: Desmopressin Acetate Injection is often used to treat mild forms of VWD. This involves injection of Desmopressin Acetate into the vein of patients to trigger the release of VWF proteins into the blood and increase levels of VWF. Desmopressin Acetate Nasal Spray is also available to be used for the same effect [3].
Type 2 and Type 3: Factor Replacement Therapy is used for more severe forms of VWD and involves the use of recombinant VWF as well as medicines with high levels of VWF. These treatments are administered via injection in the vein in the arm [3].
VWF GeneThe VWF gene extends across 178 kilobases on Chromosome 12 [5]. The complete DNA sequence of the pre-protein consists of a 2813 amino acid reading frame [4]. Large DNA deletions in the VWF gene have been identified and suggested as the basis for VWD development [5]. It has also been theorized that missense mutations occurring in a mid-section cluster of the VWF gene may be responsible for the disorder [5]. It is currently unknown all the specific mechanisms of gene alteration that play a role in the disease development.
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References:
[1] Centers for Disease Control and Prevention. (2023b, July 7). What is von willebrand disease?. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/vwd/facts.html
[2] Centers for Disease Control and Prevention. (2023a, July 7). How von Willebrand disease is inherited. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/vwd/inherited.html#:~:text=Autosomal%20dominant%20VWD%20is%20caused,parent%20who%20has%20the%20disorder
[3] Berber E. (2012). The molecular genetics of von Willebrand disease. Turkish journal of haematology : official journal of Turkish Society of Haematology, 29(4), 313–324. https://doi.org/10.5505/tjh.2012.39205
[4] NHS. (n.d.). NHS choices. https://www.nhs.uk/conditions/von-willebrand-disease/#:~:text=VWD%20is%20often%20caused%20by,from%201%20or%20both%20parents
[5] Ginsburg D. (1991). The von Willebrand factor gene and genetics of von Willebrand's disease. Mayo Clinic proceedings, 66(5), 506–515. https://doi.org/10.1016/s0025-6196(12)62393-3
[6] VWD inheritance. Haemophilia Foundation Australia. (2024, February 1). https://www.haemophilia.org.au/bleeding-disorders/von-willebrand-disease/vwd-inheritance/
[1] Centers for Disease Control and Prevention. (2023b, July 7). What is von willebrand disease?. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/vwd/facts.html
[2] Centers for Disease Control and Prevention. (2023a, July 7). How von Willebrand disease is inherited. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/vwd/inherited.html#:~:text=Autosomal%20dominant%20VWD%20is%20caused,parent%20who%20has%20the%20disorder
[3] Berber E. (2012). The molecular genetics of von Willebrand disease. Turkish journal of haematology : official journal of Turkish Society of Haematology, 29(4), 313–324. https://doi.org/10.5505/tjh.2012.39205
[4] NHS. (n.d.). NHS choices. https://www.nhs.uk/conditions/von-willebrand-disease/#:~:text=VWD%20is%20often%20caused%20by,from%201%20or%20both%20parents
[5] Ginsburg D. (1991). The von Willebrand factor gene and genetics of von Willebrand's disease. Mayo Clinic proceedings, 66(5), 506–515. https://doi.org/10.1016/s0025-6196(12)62393-3
[6] VWD inheritance. Haemophilia Foundation Australia. (2024, February 1). https://www.haemophilia.org.au/bleeding-disorders/von-willebrand-disease/vwd-inheritance/
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