von Willebrand Factor Antigen (Factor VIII:R Antigen)

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 that is largely normal or mildly decreased, with vWF:RCo of less than 30-40% (vWF:RCo/vWF:Ag ratio < 0.7), is typical for vWD 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:

• Hypothyrosis

• 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

• Inflammation

• Cancer

• Obesity

• Postoperative period

• Diabetes

• Atherosclerosis and atherothrombosis

• Pregnancy

Specimen: Citrated plasma

Collection: Tube with sodium citrate 3.2% citrate, blue top

Centrifugation: 2000-2500 g for 15 min or similar regime to produce platelet-poor plasma

Storage: Up to 6 hours at +18-25°C or plasma sample should be frozen; specimen is stable for 1 month at -20°C; whole blood after collection should not be stored at refrigerator temperatures (+2°C to +4°C) owing to cold-induced binding of vWF to platelets and selective loss of vWF:Ag in plasma. ^[3]

Description

vWF is a multimeric protein (molecular weight varies from 500-20,000 kDa) 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. ^[4] 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:Ag assay evaluates the total protein amount in plasma. The most common in clinical laboratories are latex immunoturbidimetric assays, in which the agglutination of latex microparticles coated with anti-vWF antibodies is proportional to vWF:Ag. Cloudy plasma may result in underestimation of vWF:Ag levels, while the presence of rheumatoid factor in the plasma can produce overestimation.

Indications/Applications

vWF:Ag (in conjunction with vWF:RCo and factor VIII activity) is indicated for the following:

• Diagnosis of vWD

• Differentiation of vWD subtypes

• Differentiation of vWD from hemophilia A

• Monitoring therapy of vWD

Considerations

Repeated vWF:Ag and vWF:RCo activity testing is sometimes needed to identify low levels of vWF compatible with vWD. A retrospective study showed that about 30% of pediatric patients required a second vWD test before the diagnosis was established. ^[5] Other tests (vWF collagen-binding assay, vWF multimer analysis, genetic analysis) may also be useful in confirming the diagnosis. ^{[4, 6, 7]}  African Americans have vWF:Ag levels that are approximately 20% higher than those in the white population, although their vWF:RCo levels do not differ. ^[8]  In addition, vWF:Ag increases with age, both in healthy individuals and in those with vWD. ^{[9, 10]}

A study by Ladikou et al indicated that patients with coronavirus disease 2019 (COVID-19) commonly have high levels of vWF and factor VIIIc, which may play a role in the hypercoagulable state and increased venous thromboembolism (VTE) rate encountered in COVID-19. In the report, which included 24 COVID-19 patients from the intensive care unit (ICU) or high-acuity ward, the median vWF:Ag level was found to be 350%. ^[11]

A meta-analysis of 17 publications, by Andrianto et al, confirmed that the mean vWF:Ag level in COVID-19 patients was elevated, at 306%, with deceased COVID-19 patients found to be carrying the highest concentration of the antigen (449%). ^[12]