To help determine the cause of unexplained excessive or repeated episodes of bleeding, to diagnose von Willebrand disease (VWD), and to distinguish between different types of VWD
von Willebrand Factor
A blood sample drawn from a vein in your arm
Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together, and in sequence, to stop bleeding within the body. VWF testing measures the amount of the protein present in blood and determines how well the protein functions.
Normally, when a blood vessel is damaged and bleeding begins, VWF forms an adhesive bridge between activated cell fragments called platelets and the injury site. This is followed by the clumping (aggregation) of platelets at the site and a series of actions referred to as activation of the coagulation cascade, resulting in the formation of a stable blood clot.
VWF further affects clotting by influencing the availability of coagulation factor VIII. VWF carries factor VIII in the blood, increases its half-life, and releases it as necessary. If the amount of functional VWF is insufficient, then platelet adherence and aggregation are affected, levels of factor VIII could be decreased, blood clot formation takes longer, and therefore bleeding is prolonged. This deficiency causes a condition referred to as von Willebrand disease (VWD).
VWD is the most common inherited bleeding disorder. It is a group of conditions associated with prolonged bleeding due to deficient and/or defective VWF. VWD is separated into different types and sub-types, including:
- Type 1 – with this type of VWD, there is a decrease in the amount of VWF produced, but the VWF functions normally. Levels of factor VIII are also typically low but may be normal. This is the most common type of VWD, accounting for about 75% of cases. It tends to cause bruising and mild to moderate bleeding, such as persistent nosebleeds, heavy menstrual periods, and prolonged bleeding following childbirth, trauma, dental procedures, and surgeries. Symptoms and the severity of bleeding will vary from person to person and from episode to episode.
- Type 2 – this type is associated with a normal amount of VWF, but the VWF does not function normally. Bleeding may be more severe with this with this type. Type 2 is further divided into Types 2A, 2B, 2M, and 2N.
- Type 3 – this rare type is associated with very little VWF production, very low factor VIII levels, and moderate to severe symptoms. It is often detected in infancy because of early bleeding episodes.
Rarely, VWD may be due to an acquired VWF deficiency, where there is no family or personal bleeding history up to the point when signs and symptoms develop.
Von Willebrand factor testing includes VWF antigen, which measures the amount of VWF, and VWF activity (also known as Ristocetin Cofactor), which evaluates the function of VWF. Some laboratories may offer a panel that includes both of these tests along with a factor VIII activity test.
How is the test used?
Von Willebrand factor (VWF) testing is used to investigate excessive or recurrent bleeding episodes or a personal or family history of excessive bleeding. Testing is used to help diagnose von Willebrand disease (VWD) and distinguish between the various types of VWD.
Two types of tests may be used:
- VWF antigen – this test measures the amount of the VWF protein present in the blood.
- VWF activity (also called Ristocetin Cofactor) – this test determines whether the protein is functioning properly.
These tests may be ordered by themselves or along with a coagulation factor VIII activity test and following other bleeding disorder tests, such as a complete blood count (CBC), platelet count, platelet function tests (e.g., platelet aggregation, etc.), PT (prothrombin time), and/or PTT (partial thromboplastin time).
Other tests may be ordered following VWF testing for more information and to distinguish between subtypes. These may include:
- Ratio of VWF:RCo to VWF:Ag
- Factor VIII binding assay
- Platelet VWF studies
- Collagen binding activity assay
- Ristocetin-induced platelet aggregation (RIPA) or platelet binding
- VWF propeptide (VWFpp) to VWF antigen ratio
- Molecular genetic testing for VWD (e.g., to confirm Type 2N and Type 3)
- Multimeric analysis – VWF is a protein complex that exists as "multimers" of different size. This test looks at the distribution of different sizes to help distinguish between Type 2 subtypes.
When is it ordered?
VWF testing is ordered after initial screening tests for a bleeding disorder (such as platelet function tests, PT, PTT) have been performed to investigate someone's personal or family history of excessive or recurrent bleeding episodes. The signs and symptoms that may prompt testing vary depending on the type of VWD an individual has and may include:
- Frequent or repeated nose bleeds
- Excessive bleeding from the gums after dental procedures
- Excessive bruising after minor knocks or injuries
- Heavy and/or prolonged menstrual bleeding in women
- Blood in urine or stool
- Prolonged bleeding after surgery
VWF tests may intermittently be normal in patients with VWD and should be repeated when they are initially normal but suspicions of VWD remain high. Repeat testing should be done after more than 2 weeks to confirm or exclude the diagnosis.
When VWF testing suggests VWD, additional testing may be performed to determine which subtype the person has.
What does the test result mean?
Interpretation of VWF test results can be challenging and may require consultation with a doctor who specializes in bleeding disorders, such as a hematologist or coagulation specialist, especially when determining subtypes. People who have mild VWD may have normal VWF antigen and VWF activity test results, and people who do not have VWD may have moderately decreased test results.
In a person with normal or near normal bleeding disorder screening test results, a significantly decreased VWF antigen test suggests that the person tested has a quantitative VWF deficiency and may have Type 1 VWD or, more rarely, may have acquired VWD.
Using VWF antigen results along with the VWF activity (Ristocetin Cofactor) and factor VIII coagulant activity give the optimal combination for diagnosis and management. If the VWF antigen test is normal or nearly normal and the VWF activity (Ristocetin Cofactor) is decreased, then the person may have Type 2 VWD. Further testing (e.g., VWF multimeric analysis) will be required to determine which subtype is present.
If no or very little VWF and factor VIII are present, then the person may have Type 3 VWD. This will typically be seen in a child who experiences bleeding episodes early in life. It may appear to be due (or actually be due) to hemophilia A, a factor VIII deficiency bleeding disorder that affects males.
Increased concentrations of VWF antigen and VWF activity are not considered diagnostic. VWF is one of many acute phase reactants. This means that levels will be temporarily increased with infections, inflammation, trauma, and with physical and emotional stressors. They are also increased with pregnancy and with the use of estrogen medications such as oral contraceptives.
Can VWF testing be performed in my doctor's office?
If I have heavy menstrual periods, do I have von Willebrand disease (VWD)?
It is possible, but many women who experience heavy bleeding during menstruation do not have VWD.
Can I have VWD and not know it?
Yes. Some people experience no or few symptoms, even though they have quantitative or qualitative VWF deficiencies.
Should I tell my other doctors I have von Willebrand disease?
Yes. This is important information for your healthcare providers, including your dentist, to have. They will need to plan ahead for any surgeries, childbirths, or dental procedures you may have.
Is there treatment for VWD?
Yes, there is treatment that can be given intermittently, primarily before procedures that may trigger bleeding. There is a medication called desmopressin (DDAVP) that promotes the release of VWF in some people with VWD. In addition, recombinant von Willebrand factor was approved by the US Food and Drug Administration (FDA) in December 2015. There are also VWF/FVIII concentrate replacement therapies when the recombinant is ineffective or contraindicated and there are other non-VWF related measures that can be taken to control bleeding.
Are there other causes of VWF deficiency besides inherited causes?
Yes, a deficiency in VWF may be due to another disease or condition, where there is no family or personal bleeding history up to the point when signs and symptoms develop, but this rarely occurs. It is sometimes seen in people with:
• Conditions that cause the breakdown of VWF, such as increased pressure in the arteries leading from the heart to the lungs (pulmonary hypertension) and structural defects of the heart (e.g., aortic valve stenosis)
• Myeloproliferative neoplasms associated with increased platelet production that cause increased binding of VWF to platelets
• Hypothyroidism, which can decrease VWF production
• Wilms tumor and other disorders that bind to VWF and remove it from the blood
• Certain medications such as valproic acid, ciprofloxacin, hetastarch
Is there anything else I should know?
A person's ABO blood group affects VWF concentrations. People with type O blood have VWF levels that are up to 25% lower than those with other blood types.
Measuring levels of other acute phase reactants such as CRP and fibrinogen may be helpful if VWF levels are borderline normal. For example, a borderline normal VWF with significantly high CRP and/or fibrinogen may suggest VWD.
VWF is produced by megakaryocytes and by the endothelial cells that line blood vessels. It is released by platelets and endothelial cells as needed.