von Willebrand Factor Antigen (Factor VIII:R Antigen)
- Author: Vadim Kostousov, MD; Chief Editor: Eric B Staros, MD more...
Reference ranges are as follows[1, 2] :
- Newborn < 6 mo: 60-190% (blood type O); 75-230% (non-O blood type)
- Children 1-10 years: 50-150% (blood type O); 60-160% (non-O blood type)
- Adults: 60-160% (blood type O); 70-200% (non-O blood type)
von Willebrand factor (vWF) deficiency – Inherited (von Willebrand disease [vWD])
Type 1 vWD: Decreased vWF antigen (vWF:Ag) and vWF ristocetin cofactor (vWF:RCo) levels (vWF:RCo/vWF:Ag ratio >0.7)
Type 2 vWD: vWF:Ag is largely normal or mildly decreased, while vWF:RCo less than 30-40% (vWF:RCo/vWF:Ag ratio < 0.7) is typical for vWD types 2A and 2B
Type 3 vWD: Severe deficiency or absence (both vWF:Ag and vWF:RCo < 5%)
vWF deficiency – Acquired (acquired vWD or von Willebrand syndrome)
Due to autoimmune clearance or inhibition, as follows:
- Lymphoproliferative diseases (lymphoma, leukemia)
- Monoclonal gammopathies (multiple myeloma, Waldenstrom macroglobulinemia)
- Systemic lupus erythematosus and other autoimmune disorders
- Some cancers (Wilms tumor, Ewing sarcoma, carcinoma)
Due to increased shear-induced proteolysis (vWF:Ag is often normal or even elevated), as follows:
- Ventricular septal defect
- Aortic stenosis
- Primary pulmonary hypertension
- Extracorporeal life support
- Due to other or unknown mechanisms, as follows:
- Drug-induced (hydroxyethyl starch, valproic acid)
- Myeloproliferative diseases (polycythemia, thrombocythemia)
- Angiodysplasia, glycogen storage disease
Increased vWF:Ag level and vWF:RCo activity are observed in acute phase reactions, as follows:
- Stress and extensive exercise
- Postoperative period
- Atherosclerosis and atherothrombosis
Collection and Panels
Specimen: Citrated plasma
Collection: Tube with sodium citrate 3.2% citrate, blue top
Centrifugation: 2000-2500 g for 15 min or similar regimen to produce platelet-poor plasma
Storage: Up to 6 hours at +18-25C° or plasma sample should be frozen; specimen is stable for one month at -20C°; whole blood after collection should not be stored at refrigerator (+2C° to +4C°) owing to cold-induced binding von Willebrand factor (vWF) to platelets and selective loss of vWF antigen (vWF:Ag) in plasma.
von Willebrand factor (vWF) is multimeric protein (molecular weight varies from 500-20,000 kd) that is assembled from identical monomers in endothelial cells and megakaryocytes and can be released from endothelium and platelets upon activation. The half-life of vWF is approximately 12 hours (range, 9-15 h), and its clearance is faster in persons with blood type 0. The main function of vWF is to support platelet adhesion to injured subendothelium in order to form a hemostatic plug. In addition, vWF is a carrier protein for factor VIII and prevents its proteolytic degradation in plasma.
The vWF antigen (vWF:Ag) assay evaluates the total protein amount in plasma. The most common in clinical laboratories are latex immunoturbidimetric assays for which the agglutination of latex microparticles coated with anti-vWF antibodies is proportional to vWF:Ag.
vWF:Ag (in conjunction with vWF ristocetin cofactor [vWF:RCo] and factor VIII activity) is indicated for the following:
- Diagnosis of von Willebrand disease (vWD)
- Differentiation of vWD subtypes
- Differentiation of vWD from hemophilia A
- Monitoring therapy of vWD
Lipemic specimens may result in an underestimated vWF level.
A specimen with rheumatoid factor may result in an overestimated vWF.
Repeated vWF:Ag and vWF:Rco activity testing is sometimes needed to identify low levels of vWF compatible with vWD. Other tests (vWF collagen-binding assay, vWF multimer analysis, genetic analysis) might be useful to confirm the diagnosis.[4, 5, 6]
Klarmann D, Eggert C, Geisen C, Becker S, Seifried E, Klingebiel T, et al. Association of ABO(H) and I blood group system development with von Willebrand factor and Factor VIII plasma levels in children and adolescents. Transfusion. July 2010. 50(7):1571-80. [Medline].
Appel IM, Grimminck B, Geerts J, Stigter R, Cnossen MH, Beishuizen A. Age dependency of coagulation parameters during childhood and puberty. J Thromb Haemost. 2012 Nov. 10(11):2254-63. [Medline].
Favaloro EJ, Soltani S, McDonald J. Potential laboratory misdiagnosis of hemophilia and von Willebrand disorder owing to cold activation of blood samples for testing. Am J Clin Pathol. 2004 Nov. 122(5):686-92. [Medline].
[Guideline] 4. Nichols WL, Hultin MB, James AH, Manco-Johnson MJ, Montgomery RR, Ortel TL, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia. 2008 Mar. 14(2):171-232. [Medline]. [Full Text].
Federici AB, Lee CA, Berntorp EE. Lillicrap D, Montgomery RR, eds. Von Willebrand Disease: Basic and Clinical Aspects. Wiley-Blackwell; April 2011.
Castaman G, Hillarp A, Goodeve A. Laboratory aspects of von Willebrand disease: test repertoire and options for activity assays and genetic analysis. Haemophilia. 2014 May. 20(Suppl 4):65-70. [Medline].