At a Glance
Why Get Tested?
To help determine the cause of excessive or episodic bleeding, to diagnose von Willebrand's disease (vWD), and to distinguish between different types of vWD
When to Get Tested?
When you have a personal or family history of heavy, prolonged, and/or spontaneous bleeding; when your doctor suspects you may have a bleeding disorder
Sample Required?
A blood sample drawn from a vein in your arm
Test Preparation Needed?
None
The Test Sample
What is being tested?
Von Willebrand factor (vWF or VWF) testing measures the quantity and/or function of von Willebrand factor. VWF is a protein and is one of several components that work together, and in sequence, to stop bleeding. Normally, when a blood vessel is damaged, 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 there is not enough functional VWF, then platelet adherence and aggregation are compromised, levels of factor VIII could be decreased, blood clot formation takes longer, and therefore bleeding is prolonged. This results in a condition referred to as von Willebrand's 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 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 neoplasms associated with increased platelet production that cause increased platelet binding
- 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
Von Willebrand factor tests include 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 sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
The Test
How is it used?
VWF antigen and VWF activity (Ristocetin Cofactor) tests are usually ordered by themselves, or along with a coagulation factor VIII activity test, following other bleeding disorder tests, such as a CBC (Complete Blood Count), platelet count, platelet function tests (e.g., platelet aggregation, etc.), PT (Prothrombin time), and/or PTT (Partial Thromboplastin Time). VWF testing is primarily ordered to investigate bleeding episodes or a personal or family history of excessive bleeding and to help diagnose von Willebrand's disease (vWD or VWD).
If one of the VWF tests is abnormal or they are normal but suspicion of VWD is still high, then VWF testing may be repeated. 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 antigen and VWF activity (Ristocetin Cofactor) tests are ordered by themselves or along with a factor VIII test after initial bleeding disorder screening tests (such as platelet function tests, PT, PTT) have been performed to investigate someone's personal or family history of bleeding episodes. VWF tests may be repeated when they are initially normal but suspicions of VWD remain high.
When VWF testing suggests VWD, then 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. 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 and may appear to be due (or actually be due) to hemophilia A, a factor VIII deficiency bleeding disorder that affects males.
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 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 estrogen 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% 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
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Article Sources
NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Yawn, B. et. al.(2009 December 1) Diagnosis and Management of Von Willebrand Disease: Guidelines for Primary Care. American Family Physician [On-line information]. Available online at http://www.aafp.org/afp/2009/1201/p1261.html through http://www.aafp.org. Accessed February 2010.
Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 280.
Wu, A. (© 2006). Tietz Clinical Guide to Laboratory Tests, 4th Edition: Saunders Elsevier, St. Louis, MO. Pp 1144-1145.
Rodgers, III, G. and Smock, K. (Updated 2009 August). von Willebrand Disease – vWD. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/vWD.html?client_ID=LTD through http://www.arupconsult.com. Accessed February 2010.
(Revised 2009 May). What Is von Willebrand Disease? National Heart Lung and Blood Institute [On-line information]. Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/vWD/vWD_WhatIs.html through http://www.nhlbi.nih.gov. Accessed February 2010.
Geil, J. (Updated 2009 May 21). Von Willebrand Disease. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/959825-overview through http://emedicine.medscape.com. Accessed February 2010.
Goodeve, A. and James, P. (2009 June 4). von Willebrand Disease. GeneReviews [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene∂=von-willebrand through http://www.ncbi.nlm.nih.gov. Accessed February 2010.
Mayo Clinic Staff (2009 February 7). Von Willebrand disease. MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/health/von-willebrand-disease/DS00903 through http://www.mayoclinic.com. Accessed February 2010.
George, J. (Revised 2009 May). Von Willebrand's Disease. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec11/ch133/ch133h.html#sec11-ch133-ch133h-410 through http://www.merck.com. Accessed February 2010.
Grund, S. (Updated 2008 March 21). Von Willebrand disease. MedlinePlus Medical Encylopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000544.htm. Accessed February 2010.
Link, R. (Updated 2009 March 4). Bleeding Disorders, Frequently Asked Questions. Womenshealth.gov [On-line information]. Available online at http://www.womenshealth.gov/faq/bleeding-disorders.cfm through http://www.womenshealth.gov. Accessed February 2010.
Clarke, W. and Dufour, D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 236-237.
Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007 pp 760-762.
