What is being tested?

Von Willebrand factor (vWF) testing measures the quantity of the protein present in the blood and how well it functions. vWF is a blood-clotting protein and one of several components that work together and in sequence to stop bleeding by forming a blood clot. Normally, when a blood vessel is damaged, vWF first forms an adhesive bridge between activated cell fragments known as blood platelets and the injury site. Next, it enables the platelets to clump together. Then follows a series of actions that are referred to as 'activation of the coagulation cascade'. vWF further helps clotting through another protein, coagulation factor VIII. vWF carries factor VIII in the blood, increases its half-life, and releases it as necessary. If there is not enough functional vWF, platelet adherence and aggregation are compromised, levels of factor VIII can be decreased, blood clot formation takes longer, and bleeding is prolonged. This results in a condition referred to as von Willebrand's disease (vWD).

vWD is the most commonly 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 per cent of cases. It tends to cause bruising and mild to moderate bleeding; examples include, persistent nosebleeds, heavy menstrual periods and prolonged bleeding following childbirth, trauma, dental and surgical procedures. Symptoms and the severity of bleeding 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 type. Type 2 is subdivided into Types 2A, 2B, 2M, and 2N.
• Type 3 – this rare type is associated with little to no 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 of presentation. It is sometimes seen in patients with:

• Conditions that cause the breakdown of vWF, such as pulmonary hypertension and structural defects of the heart (such as aortic valve stenosis)
• Lymphoma, myeloma, or autoimmune disorders (such as systemic lupus erythematosus) that cause the production of vWF antibodies
• Myeloproliferative disorders associated with increased platelet production that cause increased platelet binding
• Hypothyroidism, which can decrease vWF production
• Wilms tumour and other disorders that cause vWF to be removed from the blood
• Certain medications such as valproic acid, ciprofloxacin, hetastarch

There are a number of different tests to help confirm a diagnosis of vWD. Most laboratories offer only some of these tests. Your diagnosis may need to rely on tests obtained from different laboratories.

In order to make a diagnosis of vWD your doctor will select the appropriate tests based on your bleeding history. Different tests are influenced by factors such as age, ethnicity, blood type and diet at the time of testing, as well as environmental influences. It is not uncommon for someone to require many repeated tests before a diagnosis is made due to the many variables affecting test results.

How is it used?

vWF testing is primarily ordered to investigate bleeding episodes or a personal or family history of excessive bleeding and to help diagnose and distinguish between the various types of von Willebrand's disease (vWD). Your bleeding history is the most important piece of information in regards to the selection of appropriate tests and interpreting test results. Tests measuring the amount of vWF antigen and its activity  are ordered along with a coagulation factor VIII amount and/or activity test, following other bleeding disorder tests, such as a FBC (Full Blood Count), platelet count, platelet function tests (e.g., platelet aggregation), PT (Prothrombin time), and/or PTT (Partial Thromboplastin Time).

Because of the wide range of influences on the vWF tests, when tests are abnormal or they are normal but suspicion of vWD remains high, the testing is almost always repeated. Each laboratory offers a selection of tests for screening and further investigative purposes. This means that repeated blood tests are likely to be required to confirm a diagnosis of vWD and allocate a type or subtype.

The list of tests used to assist in the diagnosis of vWD are:

Tests of vWF

• vWF:Ag is an immunoassy of von Willbebrand factors that measure the concentration of vWF protein in plasma but provides no information on its function. There are a number of different methods used by laboratories.
• vWF:Act refers to a functional assay of plasma vWF that uses a monoclonal antibody that targets the part of the vWF molecule that binds to the Gp1b receptor. Other functional vWF assays may be undertaken including:
  • vWF Collagen binding assays (vWF:CB)
  • vWF Ristocetin assays (vWF:LRCo)
• Ratio’s of vWF:Act to vWF:AG

Tests of Factor VIII

• FVIII: Ag an immunological assay of FVIII
• FVIII:C a measure of the cofactor function of FVIII
• Factor VIII binding assay

Platelet vWF studies

• Ristocetin-induced platelet aggregation (RIPA) or platelet binding

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 requested?

vWF antigen and vWF activity, and factor VIII  tests are ordered following a detailed bleeding history and after initial bleeding disorder screening tests (such as , PT, PTT) have been performed to investigate someone's personal or family history of bleeding episodes. vWF tests are repeated when they are initially normal but suspicions of vWD remain high.

The signs and symptoms that may prompt testing vary depending on the type of VWD a person has and may include:

• Frequent or repeated nose bleeds
• Excessive bruising after minor knocks or injury
• Excessive bleeding from the gums after a dental procedure
• Prolonged bleeding after surgery
• Blood in urine or stool
• Heavy and/or prolonged menstrual bleeding

When vWF testing suggests vWD, then additional testing may be performed to determine which subtype the person has.

Testing may also be requested to monitor the effectiveness of therapy such as biostate or DDAVP pre and post treatment or surgery.

What does the result mean?

Interpretation of vWF test results can be challenging and requires consultation with a doctor who specialises in bleeding disorders, such as a haematologist or coagulation specialist. 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 someone with normal or near normal bleeding disorder screening test results, a significantly decreased vWF antigen test suggests that they have a quantitative vWF deficiency and may have Type 1 vWD or, more rarely, may have acquired vWD. If no or very little vWF and factor VIII are present, the person tested may have Type 3 vWD. This will typically be seen in a child who experiences bleeding episodes early in life that may appear to be due (or actually be due) to haemophilia A, a factor VIII deficiency bleeding disorder that affects males.

If the vWF antigen test is normal or nearly normal and the vWF activity is decreased, then the person being tested may have Type 2 vWD. Further testing will be required to determine which subtype is present.

Increased concentrations of vWF antigen and vWF activity are not considered diagnostic. vWF is one of the 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 oestrogen medications such as oral contraceptives.

Is there anything else I should know?

A person's ABO blood type affects vWF concentrations. People with type O blood have vWF levels that are up to 25 per cent lower than those with other blood types.

Levels of other acute phase reactants (such as CRP, 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.

Common questions

• Should everyone be tested for vWF?

No, vWF tests are not intended to be used for general screening or for initial bleeding disorder investigation. Most people will never need to have vWF testing performed.

• Can vWF testing be performed in my doctor's office?

vWF testing must be performed in a laboratory and is often sent to a reference laboratory. It requires specialised equipment and interpretation.

• If I have heavy menstrual periods, do I have 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 that I have been diagnosed with vWD?

Yes. This is important information for your doctors and dentist to have. They will need to plan ahead for any surgical or dental procedures you may have, including childbirth.

• Is there treatment for vWD?

Yes. There is treatment that can be given intermittently, that is used primarily before surgical or dental procedures. A medication called desmopressin (DDAVP) promotes the release of vWF (von Willebrand Factor) in some people with vWD. There are also vWF/FVIII concentrate replacement therapies and other non-vWF related measures that can be taken to control bleeding.

More information

RCPA Manual: von Willebrand factor activity

RCPA Manual: von Willebrand factor Ag

RCPA Manual: von Willebrand Factor multimer

RCPA Manual: von Willebrand studies

Healthdirect Australia: von Willebrand disease