How does someone get von Willebrand disease?

September 26, 2025 •

4 min read

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1% of the population. To understand how does someone get von Willebrand disease, one must look at the genetic factors and, in rarer cases, underlying medical conditions that can cause this complex clotting issue. This comprehensive guide will explain the pathways to developing this condition.

Quick Summary

People get von Willebrand disease predominantly through genetic inheritance from one or both parents, caused by a mutation in the VWF gene; it can also be acquired later in life, though this is a very rare occurrence.

Key Points

Genetic inheritance is the main cause: Most people with von Willebrand disease (VWD) are born with it, having inherited a mutated VWF gene from a parent.
Two inheritance patterns exist: Type 1 and most type 2 VWD are inherited in an autosomal dominant pattern (requiring one affected gene), while type 3 and some type 2 forms are autosomal recessive (requiring two affected genes).
Acquired VWD is very rare: A person can develop von Willebrand syndrome later in life due to an underlying medical condition, often involving the immune system or cancer.
Symptoms vary by type: Severity of bleeding depends on the type of VWD, with type 1 being the mildest and most common, and type 3 being the most severe and rarest.
Diagnosis involves specific blood tests: Doctors use tests to measure the quantity and function of von Willebrand factor and factor VIII to diagnose the disease and determine its type.
Mutations affect VWF function: The genetic mutations either cause a quantitative deficiency (less VWF) or a qualitative defect (non-functioning VWF).

Understanding the Genetic Basis of Von Willebrand Disease

Von Willebrand disease (VWD) is a lifelong condition that is almost always inherited, meaning it is passed down through families. The core of the disease lies in a genetic mutation that affects the production or function of von Willebrand factor (VWF), a crucial protein involved in blood clotting. The gene responsible for this protein is located on an autosome (chromosome 12), not a sex chromosome, which means VWD affects males and females equally. The specific pattern of inheritance depends on the type of VWD.

Autosomal Dominant Inheritance

Most cases of VWD, specifically type 1 and the majority of type 2, follow an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of the faulty gene from one parent to develop the disorder.

One affected parent: If one parent has VWD, their child has a 50% chance of inheriting the mutated VWF gene and having the disease. The severity of the child's symptoms can be different from the parent's, as VWD can have variable expression.
Variable penetrance: The expression of VWD can also be variable, meaning some people with the gene mutation might have mild or even unnoticeable symptoms. This is a key reason why VWD can sometimes go undiagnosed in families for many years.

Autosomal Recessive Inheritance

Type 3 VWD and the specific type 2N are inherited in an autosomal recessive pattern. In this case, an individual must inherit a mutated copy of the VWF gene from both parents to have the disease.

Carrier parents: Parents of an individual with an autosomal recessive condition are typically carriers, meaning they each possess one copy of the altered gene but do not show signs or symptoms of the disease themselves.
Risk for offspring: For two carrier parents, there is a 25% chance with each pregnancy that their child will inherit both mutated genes and have VWD, a 50% chance the child will be an asymptomatic carrier like them, and a 25% chance the child will inherit two normal copies.
Most severe form: Type 3 is the rarest and most severe form of VWD, characterized by a near-complete deficiency of VWF.

Acquired Von Willebrand Syndrome: The Rare Exception

While the overwhelming majority of VWD cases are inherited, a very rare form of the condition, known as acquired von Willebrand syndrome (AVWS), can develop later in a person's life. This is not caused by an inherited genetic defect but arises as a result of an underlying medical condition.

Causes of Acquired VWD

Immune system disorders: In some autoimmune conditions, the body's immune system mistakenly produces antibodies that attack and destroy the von Willebrand factor, leading to a functional deficiency.
Blood cancers: Conditions that affect the bone marrow or immune cells, such as myeloproliferative or lymphoproliferative disorders, are sometimes associated with AVWS.
Cardiac conditions: High shear stress in some heart conditions, particularly with heart valve issues, can increase the activity of an enzyme that breaks down VWF, leading to lower-than-normal levels.

How the VWF Gene Mutation Leads to Disease

The VWF gene provides instructions for the body to produce the von Willebrand factor protein. In individuals with VWD, mutations in this gene lead to either a quantitative or a qualitative defect in the VWF protein.

Quantitative vs. Qualitative Defects

Quantitative defect (Type 1 and 3): The body produces a lower-than-normal amount of VWF, or in severe cases like type 3, almost no VWF at all.
Qualitative defect (Type 2): The body produces a normal or near-normal amount of VWF, but the protein itself does not function correctly. This can be due to various issues, such as the protein being the wrong size or unable to properly bind to platelets.

The Importance of Von Willebrand Factor

VWF performs two critical functions in the blood clotting process:

It helps platelets stick to the site of an injury on the blood vessel wall.
It acts as a carrier protein for factor VIII, another important clotting protein, protecting it from degradation.

When VWF is deficient or defective, these functions are impaired, leading to prolonged and sometimes excessive bleeding after an injury.

Comparison of Inherited VWD Types


Feature	Type 1 VWD	Type 2 VWD	Type 3 VWD
Prevalence	Most common (approx. 75%)	Second most common (approx. 15%)	Rarest (approx. 5%)
VWF Level	Low	Normal or near-normal	Very low or absent
VWF Function	Normal, but insufficient quantity	Defective (qualitative defect)	N/A (absent)
Inheritance	Autosomal Dominant	Usually Autosomal Dominant, some recessive	Autosomal Recessive
Severity	Typically mild, but can vary	Intermediate, depends on subtype	Severe

Diagnosis and Management Considerations

Getting a diagnosis for VWD can be a long process, especially for those with mild symptoms. Diagnostic tests measure the amount of VWF in the blood (VWF antigen), its function (VWF activity), and factor VIII levels. Genetic testing can also confirm the specific mutation.

Management of VWD depends on the type and severity and can involve medication to increase VWF levels (like desmopressin) or replacement therapy with clotting factor concentrates. Individuals with VWD must be cautious with certain medications, such as aspirin and NSAIDs, which can interfere with blood clotting. Living with VWD involves a proactive approach, including regular check-ups with a hematologist and educating family and friends about the condition.

Conclusion

In summary, developing von Willebrand disease is primarily the result of inheriting a mutated VWF gene from one or both parents, depending on the specific type and inheritance pattern. While rare, the condition can also be acquired later in life due to underlying health issues. Understanding the origin of VWD is critical for diagnosis, family planning, and effective management of this lifelong bleeding disorder. For those with a family history or experiencing symptoms of a bleeding disorder, consulting a healthcare professional is the first and most important step toward getting a diagnosis and creating a management plan. Further information on bleeding disorders can be found at the National Hemophilia Foundation.

Frequently Asked Questions

In cases of autosomal dominant inheritance (types 1 and most 2), the disease does not skip a generation. A person must have inherited the gene from an affected parent, even if the parent's symptoms were mild. However, in autosomal recessive inheritance (type 3 and some 2), parents can be asymptomatic carriers of the gene, meaning they pass it to their child without having the disease themselves, making it appear to skip a generation.

The likelihood depends on the inheritance pattern. For autosomal dominant VWD, a child has a 50% chance of inheriting the gene if one parent has it. For autosomal recessive VWD, if both parents are carriers, there is a 25% chance of the child inheriting the disease.

VWD is not linked to the sex chromosomes, so it affects males and females equally. However, women may be diagnosed more often because symptoms like heavy menstrual bleeding and bleeding after childbirth are more obvious.

Inherited VWD is caused by a genetic mutation passed down from parents and is present at birth, even if symptoms appear later. Acquired von Willebrand syndrome is a very rare condition that develops later in life due to another medical issue and is not genetic.

Yes, though it is rare. This can happen if a spontaneous genetic mutation occurs in the individual or if the disease is acquired later in life due to a separate medical condition.

No, while both are bleeding disorders, they are different. Hemophilia is typically an X-linked recessive disorder (mostly affecting males) involving a different clotting factor, whereas VWD is usually an autosomal dominant condition affecting males and females equally.

Certain medications can sometimes contribute to acquired von Willebrand syndrome, particularly drugs that affect the immune system or have anti-clotting effects. If you suspect a medication is impacting your bleeding, it's essential to discuss it with your doctor.