von Willebrand Factor Multimer Analysis, Plasma
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
von Willebrand factor (VWF) is a large multimeric plasma glycoprotein that performs 2 critical functions in hemostasis:
-VWF is a ligand and mediates platelet adhesion to the subendothelial matrix at the site of vessel wall injury by binding to the constitutively active platelet receptor glycoprotein (GP)-Ib, V, IX complex, and to subendothelial matrix collagen
-VWF is a carrier molecule for procoagulant factor VIII in the circulation, increasing the factor VIII half-life 5-fold. Under conditions of high shear, VWF also mediates platelet-platelet cohesion by binding to the platelet receptor GP-IIb/IIIa (integrin alpha IIb beta3)
A bleeding disorder, von Willebrand disease (VWD), occurs when VWF is quantitatively deficient or qualitatively abnormal. VWD manifests clinically as easy bruising, mucocutaneous bleeding (eg, epistaxis, menorrhagia), and bleeding after trauma or surgery. VWD is the most common of the inherited bleeding disorders, and can also occur on an acquired basis.
Plasma VWF consists of a series of multimers varying in size from dimers to multimers over 40 subunits (>10 million Daltons). The largest multimers provide multiple binding sites that can interact with both platelet receptors and subendothelial matrix sites of injury, and are the most hemostatically active form of VWF.
Inherited VvWD has been classified into 3 types:
-Type 1, typically an autosomal dominant disease, is the most common, accounting for approximately 70% of VvWD patients. It represents a quantitative deficiency of VWF of variable severity.
-Type 2, which is usually an autosomal dominant disease, is characterized by several qualitative abnormalities of vFWVFW . Four subtypes have been identified: 2A, 2B, 2M, and 2N.
-Type 3, an autosomal recessive disorder, leads to severe disease with extremely reduced or undetectable levels of VWF, as well as very low levels of factor VIII.
Acquired von Willebrand syndrome (AVWS) is associated with a number of different disease states and is caused by several different pathophysiological mechanisms, including antibody formation, proteolysis, binding to tumor cells with increased clearance, and decreased synthesis. AVWS is most frequently described in patients with dysproteinemias (including monoclonal gammopathy of undetermined significance [MGUS], multiple myeloma, and macroglobulinemia), lymphoproliferative disorders, myeloproliferative disorders (eg, essential thrombocythemia), autoimmune diseases (eg, systemic lupus erythematosus), severe aortic stenosis, gastrointestinal angiodysplasia, and hypothyroidism.
Subtyping of von Willebrand factor (VWF):
-When results of complementary laboratory tests (eg, F8A / Coagulation Factor VIII Activity Assay, Plasma; VWFX / von Willebrand Activity, Plasma; and VWAG / von Willebrand Factor Antigen, Plasma) are abnormally low or discordant.
-This test is primarily used to identify variants of type 2 VWF.
-As an aid determining appropriate treatment
The plasma von Willebrand factor (VWF) multimer analysis is a qualitative visual assessment of the size spectrum and the banding pattern of VWF multimers.
This test is used to identify variants of type 2 von Willebrand disease that have fewer of the largest multimers, have unusually large multimers, or have qualitatively abnormal "bands" that indicate an abnormal VWF structure.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
von Willebrand factor (vWF) multimer analysis is not useful if:
-The following tests are normal
- F8A / Coagulation Factor VIII Activity Assay, Plasma
- VWFX / von Willebrand Factor Activity, Plasma
- VWAG / von Willebrand Factor Antigen, Plasma
-The vWF activity:vWF antigen ratio is > or =0.8
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Budde U, Schneppenheim R: von Willebrand Factor and von Willebrand Disease. Rev Clin Exp Hematol 2001;5.4:335-368
2. Ruggeri ZM: Structure and function of von Willebrand factor: Relationship to von Willebrand’s disease. Mayo Clinic Proc 1991;66:847-861
3. Sadler JE: A revised classification of von Willebrand disease. Thromb Haemost 1994;71:520-525
4. Laffan M, Brown SA, Collins PW, et al: The diagnosis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors Organization. Haemophilia 2004;10:199-217
5. Mannucci PM: Treatment of von Willebrand’s disease. N Engl J Med 2004;351:683-694
6. Pruthi RKl: Plasma von Willebrand factor multimer quantitative analysis by in-gel immunostaining and infrared fluorescent imaging. Thromb Res 2010;126:543-549