What Triggers von Willebrand's Disease? Understanding the Causes and Influencing Factors

September 24, 2025 •

4 min read

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1 in 100 people, though many cases are mild. Understanding what triggers von Willebrand's disease requires distinguishing between its inherited genetic cause and the rare, acquired form that can develop later in life.

Quick Summary

This lifelong bleeding condition results primarily from genetic mutations passed down through families, not from an external trigger. A rare form, known as acquired von Willebrand syndrome, develops later in life due to underlying medical conditions that affect the von Willebrand factor protein.

Key Points

Primary Cause is Genetic: The most common form of VWD is inherited due to a mutation in the VWF gene and is not triggered by external factors.
Acquired Syndrome is Triggered: Rare cases of Acquired von Willebrand Syndrome (AVWS) can be triggered in adulthood by other diseases or medications.
Medical Triggers for AVWS: Underlying conditions like autoimmune disorders, heart problems (aortic stenosis), and certain cancers are known triggers for AVWS.
Medication Influences: Some drugs can affect VWF levels and activity, potentially triggering AVWS in susceptible individuals.
Symptoms Not Always Obvious: Many people with inherited VWD have mild symptoms that may only become apparent after a hemostatic challenge like surgery or dental work.
Fluctuating VWF Levels: Physiological factors such as stress, exercise, pregnancy, and age can influence VWF levels but do not cause the disease itself.

The Core Cause: Inherited Gene Mutations

At its heart, von Willebrand disease is a genetic disorder, meaning it is caused by inherited changes in the VWF gene. This gene provides the instructions for making von Willebrand factor (VWF), a critical protein responsible for proper blood clotting. When the VWF gene is mutated, the body either produces too little VWF or produces VWF that doesn't function correctly. This is the fundamental, lifelong cause for most people with the condition. It's not a trigger but an underlying, pre-existing genetic blueprint.

Patterns of Genetic Inheritance

The way the mutation is inherited depends on the specific type of VWD:

Autosomal Dominant Inheritance: Seen in most cases of Type 1 and Type 2 VWD, this means inheriting a mutated VWF gene from just one parent is enough to cause the disorder. The severity can vary significantly among family members.
Autosomal Recessive Inheritance: This pattern occurs in the most severe form, Type 3 VWD, and a small number of Type 1 and Type 2 cases. It requires inheriting a mutated gene from both parents. Often, the parents are carriers who do not show symptoms themselves.

The Three Types of Inherited VWD

The specific type of VWD determines the nature of the clotting problem:

Type 1: The most common type, where VWF levels are lower than normal. This usually causes mild symptoms.
Type 2: Involves qualitative defects where the VWF protein is present but doesn't work correctly. There are four subtypes (2A, 2B, 2M, 2N), each with different functional problems.
Type 3: The rarest and most severe form, characterized by extremely low or absent VWF. Symptoms are often significant and may involve spontaneous bleeding.

The Rare Case of Acquired von Willebrand Syndrome (AVWS)

While most VWD is inherited, some individuals develop a similar bleeding disorder later in life known as acquired von Willebrand syndrome (AVWS). This is not a genetic condition and, unlike inherited VWD, is directly triggered by an underlying medical issue or medication. In AVWS, the body begins to remove or inactivate its own VWF, leading to bleeding symptoms even if the person was previously healthy.

Medical Conditions Associated with AVWS

A number of diseases can trigger AVWS, often by affecting the immune system or destroying VWF in the bloodstream. Key examples include:

Lymphoproliferative disorders: Such as chronic lymphocytic leukemia (CLL) and certain types of lymphoma, where abnormal cells interfere with VWF.
Plasma cell disorders: Including multiple myeloma, where the body produces abnormal proteins.
Heart and vascular conditions: Valvular heart disease, especially aortic stenosis, can cause high shear stress on the blood, leading to VWF degradation. Ventricular assist devices can also cause mechanical damage to VWF.
Autoimmune diseases: Conditions like systemic lupus erythematosus (lupus) and scleroderma can trigger an immune response that targets and destroys VWF.
Solid tumors: Certain cancers, including Wilms' tumor and lung cancer, can be associated with AVWS.
Endocrine disorders: Hypothyroidism has been linked to AVWS.

Medications That Can Trigger AVWS

In some cases, the use of certain medications has been associated with the development of AVWS:

Ciprofloxacin
Griseofulvin
Valproic acid

Factors That Influence, but Don't Cause, VWD Symptoms

It is important to differentiate the cause of VWD from factors that can influence or affect the expression of symptoms in individuals who already have the condition. These factors may temporarily change VWF levels but do not cause the disease itself.

Stress and Exercise: Both physical and emotional stress can cause a temporary increase in VWF levels, which may help to reduce bleeding symptoms.
Pregnancy: During pregnancy, a woman's VWF levels typically rise, which can lead to fewer bleeding episodes.
Age: VWF levels often increase naturally with age, potentially causing a decrease in bleeding symptoms for some individuals.
Blood Type: Those with type O blood often have naturally lower VWF levels, which can sometimes make VWD symptoms more noticeable.

Inherited vs. Acquired VWD: A Comparison


Feature	Inherited von Willebrand Disease (VWD)	Acquired von Willebrand Syndrome (AVWS)
Underlying Cause	A genetic mutation in the VWF gene.	An underlying medical condition or medication.
Onset	Present from birth, though symptoms may not appear until later in life.	Develops later in life, typically during adulthood.
Family History	Often have a family history of bleeding disorders.	No family history of the disease.
Inheritance	Passed down genetically from parent to child.	Not inherited and cannot be passed on to children.
Diagnosis	Based on personal and family bleeding history, blood tests showing VWF deficiency or dysfunction.	Based on new-onset bleeding symptoms in adulthood, with blood tests showing VWF abnormalities and no relevant family history.

Conclusion: The Two Paths of von Willebrand's

In summary, the answer to what triggers von Willebrand's disease is a nuanced one. For the vast majority, the disorder is fundamentally caused by a genetic mutation, and is therefore not 'triggered' in the conventional sense, though factors like stress or pregnancy can influence symptom expression. In a small number of cases, an entirely different set of circumstances, such as another medical illness or specific medication use, can lead to the rare acquired form. Proper diagnosis is crucial for effective management, whether the condition is inherited or acquired. Individuals with a suspected bleeding disorder should consult a hematologist for a definitive diagnosis and treatment plan. For more information on von Willebrand disease, visit the CDC website.

Frequently Asked Questions

No, stress and lifestyle factors do not cause von Willebrand's disease. The condition is primarily caused by a genetic mutation. However, physiological stress or exercise can temporarily raise von Willebrand factor levels in the blood, potentially masking or influencing symptoms for a short time.

The most common, inherited form of VWD is present from birth due to a genetic mutation. Symptoms can be very mild and may not be noticed until later in life, sometimes after a surgery, injury, or heavy menstrual period.

Yes, although it is rare. It is called Acquired von Willebrand Syndrome (AVWS) and is not inherited. It can develop later in life as a result of an underlying medical condition, such as certain cancers, heart problems, or autoimmune diseases.

A variety of medical issues can cause AVWS, including lymphoproliferative disorders like lymphoma, autoimmune diseases such as lupus, heart conditions like aortic stenosis, and certain tumors.

Yes, though it is uncommon. Some medications, including ciprofloxacin and valproic acid, have been reported in association with the development of acquired von Willebrand syndrome.

It is passed down genetically through mutated copies of the VWF gene. In most cases (Type 1 and 2), a dominant inheritance pattern means one faulty gene is enough. For the most severe type (Type 3), a recessive pattern requires two faulty copies.

Not necessarily. For people with inherited VWD, symptoms can sometimes become less frequent with increasing age, as VWF levels can rise over time. For others, symptom expression can be inconsistent throughout their lives.