Von Willebrand factor (VWF) is a protein crucial to the blood clotting process. If you don’t have enough of this protein, or if it doesn’t work as it’s supposed to, you may have von Willebrand disease (VWD), a bleeding disorder.

VWD is the most common inherited bleeding disorder. Bleeding disorders disrupt your body’s typical healthy blood clotting process.

Experts estimate that VWD affects up to 1% of the population, though the number of people with serious bleeding symptoms is much lower. Affected people might notice symptoms ranging from nosebleeds and heavy periods to internal bleeding.

All cases of VWD are ultimately due to weak or improper activity of VWF, a large protein that plays a crucial role in hemostasis, the process of blood clotting.

Most cases of VWD are due to changes in the genes that make VWF. Very rarely, the disease can develop later in life, resulting from other medical conditions affecting your VWF levels and activity.

The VWF gene is located on chromosome 12. It encodes for VWF, a complex protein with several different active sites called domains. Each of these domains plays a different role in your blood clotting process.

VWF regularly circulates in your bloodstream at baseline levels. When you’re bleeding, your body releases more VWF from your platelets and the cells lining your blood vessels.

At the site of injury, each domain of VWF performs different key functions, including:

  • helping your platelets stick to the injured blood vessel and stick together, starting the blood clotting process
  • carrying and stabilizing clotting factor VIII, a protein crucial to the formation of a more durable clot to seal off the bleeding area
  • binding into large clumps, called VWF multimers, which have more active domains and are very effective at inducing clotting

Which clotting factor is VWF?

VWF isn’t a clotting factor itself, but it does interact with certain key clotting factors.

The blood clotting process is complex, involving many different proteins and cellular pathways. You have 13 numbered clotting factors (factors I through XIII), which activate in a cascade critical to forming a blood clot.

But the clotting cascade also requires many other substances besides your numbered clotting factors. For example, platelet cells, vitamin K, and VWF are all crucial to the clotting process.

VWF typically circulates in your bloodstream in a wide range of normal values. These can range from 50 to 200 international units per deciliter (IU/dL).

This is because your VWF level can vary according to your age, blood type, and other factors. Scientists have so far identified 19 different genetic loci involved in regulating plasma VWF levels. Circulating VWF is cleared rapidly from your bloodstream, with a half-life of about 16 hours, but this clearance rate is also highly variable.

A doctor might suspect VWD if you have very low VWF levels (under 30 IU/dL). They might also consider VWD at levels of 30 to 49 IU/dL if you have significant bleeding problems. Mildly low VWF levels are common in the larger population, but many people with low VWF don’t have noticeable bleeding issues.

High VWF levels may be due to genetic changes or environmental factors like inflammation. Persistently high VWF levels may be linked to a higher blood clotting risk.

When considering a bleeding disorder, a doctor will often start by performing a complete blood count and other coagulation tests. If they suspect VWD, they might order the following tests:

  • VWF antigen: This directly checks the amount of VWF in your blood.
  • VWF activity: This is indirectly checked by assessing some of the functions of VWF.
  • Factor VIII activity: This checks for factor VIII levels, which will be low if you have decreased VWF.
  • VWF activity/antigen ratio: This will be low if you have dysfunctional VWF.

Additional testing is available to distinguish the type of VWD you might have. This can include VWF multimer and propeptide levels and desmopressin challenge testing. Genetic testing might help differentiate among the type 2 VWD subtypes.

VWF is a large protein with many different functions. Scientists have identified several mutations in the VWF gene, all with different outcomes.

Your VWF levels may be low if you have genetic changes causing reduced or absent production of VWF (as seen in VWD disease types 1 and 3) or unusually rapid inactivation and clearance of VWF or VWF multimers from your bloodstream (seen in type 1 and acquired VWD).

However, you can still have VWD when your VWF levels appear typical. Some people have gene mutations that cause their body to produce ineffective or dysfunctional VWF. In this case, the VWF level appears normal, but VWF activity and effectiveness are low. This is characteristic of type 2 VWD.

VWD is the most common genetic bleeding disorder. It usually causes symptoms like excessive nose, gum, or menstrual bleeding.

All types of VWD result from inadequate activity of VWF, a large and complex protein. Although it’s not one of your numbered clotting factors, VWF is critical to the blood clotting process.

If VWD runs in your family, or you’ve received a diagnosis of VWD, you might have reduced or absent production of VWF. Gene changes might also cause your body to make an altered VWF protein that can’t perform its usual functions to help your blood clot. You might also have unusually rapid clearance of VWF from your bloodstream.

A doctor can help you understand your VWF levels and activity, as well as how this could affect your treatment plan.