von Willebrand Disease 2N (Subtype Normandy), Plasma
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosing von Willebrand disease (VWD) type 2N
Evaluating patients diagnosed with mild-to-moderate hemophilia A with an autosomal inheritance pattern
Evaluating hemophilia A patients with a shortened survival of infused factor VIII (FVIII) (not caused by a specific FVIII inhibitor)
Evaluating female patients with low FVIII activity and no prior family history of hemophilia A
Evaluating patients with Type 1 or Types 2A, 2B, or 2M VWD with FVIII activity discordantly lower than the von Willebrand factor antigen level
Highlights
This test is the most cost-effective test for diagnosis of von Willebrand Factor: Factor VIII binding defects.
Genetic tests screening for variants that cause von Willebrand disease (VWD) type 2N are available. Limitations of genetic testing include expense and the potential for variants causing VWD 2N in regions not covered by the molecular assays.
Method Name
A short description of the method used to perform the test
Enzyme-Linked Immunosorbent Assay (ELISA)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Factor VIII binding defect
Normandy Subtype (von Willebrand Disease 2N)
Von Willebrand Disease 2N (Subtype Normandy)
VWD Type 2N
Specimen Type
Describes the specimen type validated for testing
Plasma Na Cit
Additional Testing Requirements
VWAG / von Willebrand Factor Antigen, Plasma; VWACT / von Willebrand Factor Activity, Plasma; and F8A / Coagulation Factor VIII Activity Assay, Plasma are recommended to supplement results of this test.
Necessary Information
If performed at another laboratory, forward the results of the following tests with the specimen:
-von Willebrand factor antigen
-VWF activity (ristocetin cofactor, latex immunoassay etc)
-Factor VIII activity
These results aid in the interpretation of this test.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Specimen Type: Platelet-poor plasma
Collection Container/Tube: Light-blue top (3.2% sodium citrate)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. For complete instructions, see Coagulation Guidelines for Specimen Handling and Processing
2. Centrifuge, transfer all plasma into a vial, and centrifuge plasma again.
3. Aliquot plasma into a separate tube leaving 0.25 mL in the bottom of the centrifuged vial.
4. Freeze plasma immediately (no longer than 4 hours after collection) at -20 degrees C or, ideally, less than or equal to -40 degrees C.
Additional Information:
1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.
2. Each coagulation assay requested should have its own vial.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
0.5 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | OK |
| Gross lipemia | OK |
| Gross icterus | OK |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Plasma Na Cit | Frozen | 56 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosing von Willebrand disease (VWD) type 2N
Evaluating patients diagnosed with mild-to-moderate hemophilia A with an autosomal inheritance pattern
Evaluating hemophilia A patients with a shortened survival of infused factor VIII (FVIII) (not caused by a specific FVIII inhibitor)
Evaluating female patients with low FVIII activity and no prior family history of hemophilia A
Evaluating 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 disease-causing 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. Disease-causing 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 that 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 out of 1198 (4.8%) 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:
-Genetic counseling differs considerably from that for X-linked recessive HA since the inheritance of VWD2N is autosomal recessive.
-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 a 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 to factor VIII (FVIII) binding 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 antirabbit 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 to factor VIII binding ratio 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;17(6):944-951. doi:10.1111/j.1365-2516.2011.02499.x
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;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;76(3):372-379. doi:10.1111/j.1365-2141.1990.tb06371.x
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;76(4):598-602
5. Seidizadeh O, Peyvandi F, Mannucci PM. Von Willebrand disease type 2N: an update. J Thromb Haemost. 202119(4):909-916. doi:10.1111/jth.15247
Method Description
Describes how the test is performed and provides a method-specific reference
The von Willebrand factor (VWF):factor VIII (FVIII) B assay utilizes enzyme linked immunosorbent assay technology. A diluted plasma sample adjusted to 10 IU dL of VWF:antigen is incubated with a rabbit antihuman VWF F(ab')2, which is coated on the internal walls of the microplate wells. The factor VIII of the tested plasma dissociated during the incubation is washed away. Recombinant FVIII (FVIIIr) is then added, which binds to VWF. Next, mouse monoclonal antihuman FVIII antibody coupled with peroxidase binds to the remaining free antigenic determinants of the bound FVIIIr. Bound FVIIIr is quantified using a peroxidase-conjugated mouse antihuman FVIII monoclonal antibody. The intensity of the color is directly proportional with the concentration of VWF:FVIIIB initially present in the plasma sample.(Package insert: Asserachrom VWF:FVIIIB. Diagnostica Stago; 03/2014)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Monthly on the third Thursday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
85246
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| VWD8B | VWD 2N (Normandy), P | 90919-2 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 607336 | VWF:FVIIIB | 90919-2 |
| 607337 | VWF:FVIIIB Interpretation | 48595-3 |