What Clotting Factor Is Deficient in Von Willebrand Disease? Understanding VWF and its Role

October 1, 2025 •

3 min read

Affecting up to 1% of the U.S. population, von Willebrand disease (VWD) is the most common inherited bleeding disorder. At the heart of this condition is a problem with blood clotting, making the question of what clotting factor is deficient in von Willebrand disease central to understanding its effects. The primary issue is with the von Willebrand factor (VWF) itself, though this can also indirectly lead to a deficiency of another key clotting protein, Factor VIII (FVIII).

Quick Summary

Von Willebrand disease is caused by a deficient or defective von Willebrand factor (VWF). In many cases, this primary issue also causes a secondary deficiency in Factor VIII, which leads to impaired blood clotting.

Key Points

Primary Deficiency: The core problem in von Willebrand disease is a deficiency or functional defect in the protein known as von Willebrand factor (VWF).
Secondary Factor VIII Deficiency: Because VWF normally carries and protects Factor VIII (FVIII), a primary VWF issue can lead to a secondary, variable deficiency of FVIII.
Three Main Types: VWD is classified into three main types based on the nature of the deficiency: Type 1 (partial VWF deficiency), Type 2 (qualitative VWF defect), and Type 3 (severe VWF deficiency).
Similarities to Hemophilia A: Severe VWD, particularly Type 2N, can cause low FVIII levels that mimic hemophilia A, but the underlying cause and inheritance patterns differ.
Diagnosis is Multifaceted: Diagnosing VWD requires several specialized tests to measure VWF amount (antigen), VWF function, and FVIII levels, not just one simple test.
Management is Subtype-Specific: Treatment varies significantly by VWD type, ranging from medications like desmopressin to replacement therapy with VWF/FVIII concentrates.

The Primary Deficiency: von Willebrand Factor (VWF)

Von Willebrand disease (VWD) is an inherited condition caused by issues with von Willebrand factor (VWF), a protein crucial for blood clotting. This issue can mean either not having enough VWF or having VWF that doesn't work correctly.

VWF helps with blood clotting in two main ways:

Platelet Adhesion: It helps platelets stick to damaged blood vessel walls to start forming a clot.
Carrying Factor VIII: It carries and protects Factor VIII (FVIII), another important clotting factor, preventing it from breaking down too quickly in the blood.

The Secondary Effect: Low Factor VIII (FVIII)

Because VWF carries and protects FVIII, a problem with VWF can also lead to lower levels of FVIII. Without enough functional VWF, FVIII is removed from the bloodstream faster. This can worsen bleeding issues, especially in more severe forms of VWD like Type 3.

A Spectrum of Deficiencies: Types of von Willebrand Disease

VWD exists in different types, based on the specific problem with VWF.

Type 1 VWD

Cause: Not enough VWF, but the VWF present works fine.
Frequency: Most common type, making up 60%-80% of cases, and usually mild.
FVIII Levels: May be low, but typically not severely so.

Type 2 VWD

Cause: Enough VWF is made, but it doesn't work correctly. There are four subtypes (2A, 2B, 2M, 2N).
Frequency: Accounts for 15%-30% of cases.
Subtype 2N: This specific type has a problem with VWF binding to and protecting FVIII, leading to significantly low FVIII. It can sometimes resemble hemophilia A.

Type 3 VWD

Cause: Very little or no VWF is produced.
Frequency: Rarest and most severe type, affecting 5%-10% of patients.
FVIII Levels: Results in a severe FVIII deficiency, causing significant bleeding similar to hemophilia, including bleeding into joints and muscles.

Diagnosis and Management of VWD

Diagnosing VWD involves blood tests such as:

VWF Antigen: Measures the amount of VWF.
VWF Activity: Checks how well VWF functions.
Factor VIII Clotting Activity: Measures the amount and function of FVIII.
VWF Multimer Analysis: Helps identify the specific VWD type, especially for Type 2.

Treatment depends on the VWD type and severity and can involve medications like desmopressin or replacement therapies with VWF and FVIII concentrates.

Comparing VWD and Hemophilia A

It's important to distinguish VWD, particularly Type 2N, from Hemophilia A, as both can involve low FVIII but for different reasons.


Feature	Von Willebrand Disease (VWD)	Hemophilia A
Primary Cause	Deficiency or defect in von Willebrand Factor (VWF)	Deficiency or defect in Factor VIII (FVIII)
Secondary Effect	Can cause a secondary, variable deficiency of FVIII due to VWF's protective role	No secondary deficiency of VWF
Inheritance Pattern	Typically autosomal dominant (Types 1 & 2), autosomal recessive (Type 3)	X-linked recessive, primarily affects males
Bleeding Type	Primarily mucocutaneous (mucous membranes and skin), such as nosebleeds, easy bruising, and heavy menstrual bleeding	Deeper tissue bleeding, especially into joints (hemarthrosis) and muscles
Prevalence	Most common inherited bleeding disorder, affecting up to 1% of the U.S. population	Less common than VWD
Treatment Difference	Often requires replacement of both VWF and FVIII, especially in severe types	Replaces FVIII only

Conclusion

The main clotting factor issue in von Willebrand disease is a problem with the von Willebrand factor (VWF). This can lead to a secondary deficiency of Factor VIII, which VWF helps protect. The type and severity of VWD determine the extent of these deficiencies and the resulting bleeding symptoms. Accurate diagnosis through specific blood tests is key to managing VWD effectively. For more information, see the National Bleeding Disorders Foundation (NBDF) at www.bleeding.org.

Frequently Asked Questions

VWD is caused by a problem with von Willebrand factor (VWF), while hemophilia A is a deficiency of Factor VIII. A key difference is that VWD can cause a secondary FVIII deficiency, but hemophilia does not affect VWF levels.

VWF acts as a carrier protein for Factor VIII (FVIII). It protects FVIII from being rapidly broken down and cleared from the blood. Without sufficient or functional VWF, FVIII is cleared quickly, leading to lower levels.

Yes, VWD is a genetic disorder. Most types (1 and 2) are inherited in an autosomal dominant pattern, while the most severe Type 3 is inherited in an autosomal recessive pattern.

Type 1 VWD is the most common and mildest form, resulting from a partial quantitative deficiency of von Willebrand factor. It accounts for up to 80% of all cases.

Common symptoms include easy bruising, frequent or prolonged nosebleeds, prolonged bleeding from cuts, heavy or long menstrual periods, and excessive bleeding after dental work or surgery.

There is no cure for von Willebrand disease, but effective treatments are available to manage symptoms and prevent or control bleeding episodes.

Diagnosis is confirmed through a series of blood tests, including measuring VWF antigen, VWF activity, and Factor VIII activity. Sometimes, genetic testing and multimer analysis are needed to determine the specific subtype.