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Test Catalog

Test ID: VWD8B    
von Willebrand Disease 2N (Subtype Normandy), Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis of von Willebrand disease (VWD) type 2N

 

Evaluation of patients diagnosed with mild-to-moderate hemophilia A with an autosomal inheritance pattern

 

Evaluation of hemophilia A patients with a shortened survival of infused factor VIII (FVIII) (not caused by a specific FVIII inhibitor)

 

Evaluation of female patients with low FVIII activity and no prior family history of hemophilia A

 

Evaluation of patients with Type 1 or Types 2A, 2B, or 2M VWD with FVIII activity discordantly-lower than the von Willebrand factor antigen level

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

von Willebrand disease (VWD) is a bleeding disorder due to quantitative or qualitative defects in von Willebrand factor (VWF), which results from pathogenic alterations in the VWF gene. VWD constitutes 1 of the 2 most common bleeding disorders. Most subtypes of VWD are inherited as autosomal dominant traits, although autosomal recessive variants occur.

 

In hemostasis, there are 2 essential roles for VWF. The first is its ability to promote platelet adhesion to damaged vessel walls, and the second is to function as a carrier protein for Factor VIII (FVIII). Thus, noncovalent binding of FVIII to VWF is necessary for normal survival of FVIII in the blood circulation. In patients with severe VWD the circulating half-life of endogenous or infused FVIII is shorter than expected. Pathogenic alterations within the FVIII binding domain of VWF may result in an isolated ‘deficiency’ of FVIII associated with a clinically mild to moderate bleeding disorder which may be misdiagnosed as Hemophilia A (HA).

 

Abnormal binding of FVIII to VWF can be detected with a binding assay. Since its initial description in patients from the Normandy region of France, more recent studies suggest that VWD type 2N or Normandy (VWD2N) has been associated with a more severe phenotype among patients who are homozygous for pathogenic alterations within the FVIII binding domain of VWF.

 

In an international survey, FVIII binding defect was detected in 58/1198 (4.8%) of patients with mild HA. Other studies confirm these findings and reveal that 1.5% to 16.6% of patients with VWD Type 1 have the FVIII binding defect. The diagnosis of VWD2N has 2 main implications: 1) genetic counseling differs considerably from that for X-linked recessive HA since the inheritance of VWD2N is autosomal recessive; and 2) optimal treatment or prophylaxis of bleeding requires factor replacement therapy with products containing functional VWF.

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.

68-106%

Pediatric reference ranges have not been established for this assay but likely achieve adult reference range by 18 years of age.

Interpretation Provides information to assist in interpretation of the test results

A reduced capacity of patient’s von Willebrand factor (VWF) to bind to recombinant factor VIII (FVIII) is consistent with von Willebrand disease (VWD) type 2N (Normandy).

 

A mild to moderate decrease of the VWF:FVIIIB ratio suggests the presence of a VWD Type 2N due to heterozygous variants in the FVIII binding domain of VWF. If clinically indicated, DNA sequence analysis of the FVIII binding domain of VWF may provide useful information.

 

Results do not exclude other variants of congenital VWD, eg, type 1, 2A, 2B or 2M or congenital hemophilia A. Clinical correlation should be made between patient and family bleeding history and results of VWF antigen, factor VIII and VWF activity assays.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The presence of anti-rabbit antibodies in certain subjects may lead to aberrant results.

 

A von Willebrand Factor (VWF) antigen level greater than or equal to 15% is necessary for a good interpretation of VWF:FVIIIB results.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Veyradier A, Caron C, Ternisien C, et al: Validation of the first commercial ELISA for type 2N von Willebrand’s disease diagnosis. Haemophilia 2011 Nov;17(6):944-951

2. Sadler JE: A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.Thromb Haemost 1994 Apr;71(4):520-525

3. Mazurier C, Gaucher C, Jorieux S, et al: Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed as heamophilia A carriers: consequences for therapy and genetic counselling. Br J Haematol 1990 Nov;76(3):372-379

4. Schneppenheim R, Budde U, Krey S, et al: Results of a screening for von Willebrand disease type 2N in patients with suspected haemophilia A or von Willebrand disease type 1. Thromb Haemost 1996 Oct;76(4):598-602

 

Special Instructions Library of PDFs including pertinent information and forms related to the test