Test ID: VWD2N
von Willebrand Disease 2N (Subtype Normandy), Blood
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Diagnosis of von Willebrand disease (vWD) Type 2N
Evaluation and genetic counseling of patients with mild-to-moderate hemophilia A with an atypical 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
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Direct Mutation Analysis by Polymerase Chain Reaction (PCR)
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Normandy Subtype (von Willebrand Disease 2N)
Von Willebrand Disease 2N (Subtype Normandy)
VWD Type 2N
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube:
Preferred: Yellow top (ACD solution B)
Acceptable: EDTA, sodium citrate
Specimen Volume: Full tube
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Additional Information: If F8A/9070 Coagulation Factor VIII Activity Assay, Plasma; VWAG/9051 von Willebrand Factor Antigen, Plasma; and/or RIST/9046 Ristocetin Cofactor, Plasma have been previously performed on the patient, include results of these tests when submitting specimen for testing.
Forms:
1. Coagulation Patient Information Sheet (Supply T675) in Special Instructions
2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross OK |
| Lipemia | Mild OK; Gross OK |
| Icterus | NA |
| Other | Green top (heparin) tube |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole blood | Ambient (preferred) | |
| Refrigerated | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Hemophilia A and von Willebrand disease (vWD) are bleeding disorders caused by quantitative or qualitative defects in factor VIII (FVIII) or von Willebrand factor (vWF), respectively, and constitute 2 of the most common bleeding disorders. Hemophilia A is inherited as an X-linked recessive disorder while most subtypes of vWD are inherited as autosomal dominant disorders.
vWF plays 2 essential roles in hemostasis. vWF mediates platelet adhesion to damaged blood vessel walls and vWF is a carrier protein for FVIII.
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 shortened.
Mutations within the vWF gene regions encoding for the FVIII binding domain of vWF may produce a phenotype of isolated FVIII "deficiency" associated with a clinically mild-to-moderate bleeding disorder which may be misdiagnosed as HA. This mild vWD phenotype was first described in patients from the Normandy region of France, vWD Normandy (vWD Type 2N). vWD Type 2N inheritance pattern is autosomal recessive.
In an international survey, vWD Normandy was detected in 58 (4.8%) of 1,198 patients previously diagnosed as having mild hemophilia A. Three vWF gene mutations (vWF Thr791Met, Arg816Trp, and Arg854Gln) accounted for 96% of patients with mutations in the FVIII binding domain of vWF.(3) Patients who are homozygous for 1 of the 3 common mutations have reduced levels of FVIII activity, whereas patients who are heterozygous typically have normal FVIII activity. However, patients who are heterozygous for 1 of the 3 common vWD Type 2N mutations may have decreased FVIII activity in the presence of a second (compound heterozygous) mutation in the vWF gene that typically results in a Type 1 or Type 3 vWD (quantitative defect). vWD Type 2N also has been associated with a more severe bleeding phenotype among patients who are homozygous for other mutations (vWF Glu24Lys) within the FVIII binding domain of vWF.(1,2)
Additional studies suggest that 1.5% (3/199) to 13.8% (5/36) of patients with vWD Type 1 have a FVIII binding defect.(2,4)
The diagnosis of vWD Type 2N is important for appropriate genetic counseling, because the inheritance of vWD Type 2N is autosomal recessive (as opposed to the X-linked recessive inheritance of HA).
Optimal treatment or prophylaxis of bleeding requires 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.
Negative
Interpretation Provides information to assist in interpretation of the test results
Interpretive report will include specimen information, assay information, background information, and conclusions based on the test results.
Clinical information and results of patient testing (factor VIII coagulant activity, von Willebrand factor antigen, and ristocetin cofactor activity) are useful for test interpretation.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
On-site Hemophilia Center, Special Coagulation, and/or Medical Genetics consultations are available for registered Mayo Clinic patients and may be especially helpful in complex cases. Phone consultations are available for Mayo Medical Laboratories clients.
This test will not detect other rare mutations within the known factor VIII binding domain of the von Willebrand factor (vWF) gene or other mutations in the vWF gene.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Tuley EA, Gaucher C, Jorieux S, et al: Expression of von Willebrand factor "Normandy": an autosomal mutation that mimics hemophilia A. Proc Natl Acad Sci USA 1991;88:6377-6381
2. Schneppenheim R, Budde U, Krey S, et al: Results of a screening for von Willebrand disease type 2N in patients with suspected hemophilia A or von Willebrand disease type 1. Thromb Haemost 1996;76:598-602
3. Mazurier C, Meyer D: Factor VIII binding assay of von Willebrand factor and the diagnosis of type 2N von Willebrand disease-results of an international survey. On behalf of the Subcommittee on von Willebrand Factor of the Scientific and Standardization committee of the ISTH. Thromb Haemost 1996;76:270-274
4. Nesbitt IM, Goodeve AC, Guilliatt AM, et al: Characterization of type 2N von Willebrand disease using phenotypic and molecular techniques. Thromb Haemost 1996;75:959-964
Method Description Describes how the test is performed and provides a method-specific reference
Direct mutation analysis: Based on the PCR, 3 regions of the von Willebrand factor gene (exons 18, 19, 20) are individually amplified from leukocyte genomic DNA. Each amplification product is restricted by an endonuclease (exon 18: Tai I [Thr791Met]; exon 19: Ava II [Arg816Trp]; exon 20: Msp I [Arg854Gln]) followed by agarose-gel electrophoresis and ethidium bromide staining of the restriction products. A Polaroid picture records information to be interpreted. (Molecular cloning: a laboratory manual. 2nd edition. Edited by J Sambrook, EF Fritsch, T Maniatis. Cold Spring Harbor, NY, Cold Spring Harbor Press, 1989, p 53)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Tuesday; 1 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
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 The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81401-VWF (von Willebrand factor) (eg, von Willebrand disease type 2N), common variants (eg, T791M, R816W, R854Q)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 21813 | von Willebrand Disease 2N Method | In Process |
| 81662 | Thr791Met | In Process |
| 15230 | Arg816Trp | 41210-6 |
| 15231 | Arg854Gln | 41209-8 |
| 21817 | VWD2N Interpretation | 69049-5 |
| 21819 | VWD2N Reviewed By | In Process |
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