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HelpTest ID VWD2N von Willebrand Disease 2N (Subtype Normandy), Blood
Useful For
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
Method Name
Direct Mutation Analysis by Polymerase Chain Reaction (PCR)
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name
von Willebrand Disease 2N (Normandy)Specimen Type
Whole bloodContainer/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 / Coagulation Factor VIII Activity Assay, Plasma; VWAG / von Willebrand Factor Antigen, Plasma; and/or RIST / 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 (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.
3.If not ordering electronically, complete, print, and send a Coagulation Test Request Form (T753) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/coagulation-test-request-form.pdf)
Specimen Minimum Volume
1 mL of blood in 3-mL ACD tube
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole blood | Ambient (preferred) | |
| Refrigerated | ||
Clinical Information
Hemophilia A (HA) 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
Negative
Cautions
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.
Day(s) Performed
Tuesday; 1 p.m.
Report Available
2 daysPerforming Laboratory
Mayo Medical Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.CPT Code Information
81401-VWF (von Willebrand factor) (eg, von Willebrand disease type 2N), common variants (eg, T791M, R816W, R854Q)