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HelpTest Code GNVWD von Willebrand Disease, VWF and GP1BA Genes, Next-Generation Sequencing, Varies
Ordering Guidance
A systematic diagnosis through conventional coagulation testing is recommended before considering genetic testing for any suspected bleeding disorder. Special coagulation testing for evaluating patients suspected of having von Willebrand disease is available; order AVWPR / von Willebrand Disease Profile, Plasma.
If testing for hereditary bleeding disorders using a larger panel is desired, both a 6-gene and a 25-gene bleeding panel are available. For more information see GNBLF / Bleeding Disorders, Focused Gene Panel, Next-Generation Sequencing, Varies or GNBLC / Bleeding Disorders, Comprehensive Gene Panel, Next-Generation Sequencing, Varies.
Customization of this panel and/or single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Targeted testing for familial variants (also called site-specific or known variants testing) is available for VWF and GP1BA genes. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Additional Testing Requirements
All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen as this must be a different order number than the prenatal specimen.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Necessary Information
von Willebrand Disease Patient Information is required. Testing may proceed without the patient information; however, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated
Prenatal Specimens
Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20 mL
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional information:
1. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid.
2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20 mg
Specimen Stability Information: Refrigerated
Additional Information:
1. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing.
2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Acceptable:
Specimen Type: Confluent cultured cells
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured cells from another laboratory.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Forms
1. von Willebrand Disease Patient Information (T825) is required.
2. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
3. If not ordering electronically, complete, print, and send an Coagulation Test Request (T753) with the specimen.
Secondary ID
619201Useful For
Evaluating von Willebrand disease and platelet-type von Willebrand disease in patients with a personal or family history suggestive of von Willebrand disease
Confirming von Willebrand disease or platelet-type von Willebrand disease diagnoses with the identification of a known or suspected disease-causing alteration in the VWF or GP1BA genes, respectively
Determining the disease-causing alterations within the VWF or GP1BA genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of von Willebrand disease or platelet-type von Willebrand disease, respectively
Subtyping von Willebrand disease as type 1 (most common), type 2 variants (less common), or type 3 (rare), as well as distinguishing von Willebrand disease from platelet-type von Willebrand disease
Identifying the causative alteration for genetic counseling purposes
Prognosis and risk assessment based on the genotype-phenotype correlations
Carrier testing for close family members of an individual with a von Willebrand disease or platelet-type von Willebrand disease diagnosis
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| CULAF | Amniotic Fluid Culture/Genetic Test | Yes | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
The laboratory workup for von Willebrand disease is complex and requires initial coagulation screening (including a complete blood cell count, platelet count, partial thromboplastin time, prothrombin time, and fibrinogen or thrombin time) should be performed prior to any consideration of genetic testing.
Genetic testing for a von Willebrand disease is indicated if:
-Coagulation tests indicate a deficiency or functional abnormality in von Willebrand factor
-There is a clinical suspicion for von Willebrand disease due to family history or atypical clinical presentation
-Acquired causes of deficiencies associated with von Willebrand disease have been excluded (eg, certain myeloproliferative disorders, plasma cell dyscrasias including monoclonal gammopathy of undetermined significance, high-shear stress-related cardiovascular conditions, and autoimmune disorders).
A clinical and laboratory testing algorithm for von Willebrand disease has been developed by the National Heart, Lung, and Blood Institute of the National Institutes of Health that is freely available at www.nhlbi.nih.gov/health-pro/guidelines/current/von-willebrand-guidelines. If von Willebrand disease is a concern, sets of clinical guidelines on testing for von Willebrand disease and platelet-type von Willebrand disease are also freely available.(1,2)
For prenatal specimens only:
Prenatal genetic testing is not routinely performed without the prior identification of familial alterations. Requests for this prenatal testing without a known familial alteration are performed at the discretion of the Molecular Hematopathology Laboratory Director.
-If amniotic fluid (nonconfluent cultured cells) is received, an amniotic fluid culture/genetic test will be added at an additional charge.
-If a chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added at an additional charge.
For any prenatal specimen that is received, maternal cell contamination testing will be performed at an additional charge.
Special Instructions
Method Name
Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
VWF and GP1BA Genes, Full Gene NGSSpecimen Type
VariesSpecimen Minimum Volume
Blood: 1 mL; Amniotic fluid: 10 mL; Other specimen types: see Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting approximately 1% of the population. VWD is a bleeding diathesis that usually involves mucous membranes and skin sites. It is typically of mild to moderate severity, although life-threatening bleeding in the central nervous system or gastrointestinal tract can occur. The most common presenting symptoms in individuals affected by VWD include epistaxis, menorrhagia, bleeding after dental extraction, postoperative bleeding, ecchymoses, bleeding from minor cuts or abrasions, gingival bleeding, and hemarthrosis.(1) While VWD occurs with equal frequency among men and women, symptoms in women are more obvious because of increased bleeding during menstrual periods, pregnancy, and after childbirth.
VWD is a result of defects in the concentration, structure, or function of von Willebrand factor (VWF), leading to decreased factor VIII (FVIII) in circulation and/or impaired platelet adhesion and aggregation at the site of vascular injury. The VWF gene encodes for VWF, a protein that protects blood clotting FVIII from degradation in circulation and promotes platelet adhesion and aggregation at the site of vascular injury. In circulation, VWF assembles into linear strings called multimers, the size of which is biologically important; larger multimers being more reactive than smaller multimers.
Levels of factor VIII, VWF antigen, and VWF activity may vary greatly within each individual over time and also with blood type (normal type "O" individuals may have VWF lower than normal individuals of other blood groups). VWF levels (and factor VIII) can be elevated in liver disease, pregnancy, estrogen therapy, inflammation, and after exercise (acute-phase reactant). VWF levels in hemophilia are normal.
This panel evaluates 2 genes associated with von Willebrand disease and platelet-type von Willebrand disease. Discrimination between these 2 heritable disorders, specifically concerning types 2A and 2B VWD and platelet-type VWD, using genetic analysis can help guide treatment. Genetic testing can also be used to assist in discriminating between type 2N VWD and hemophilia A. Subtyping of VWD using genetic analysis is important for prognosis and in guiding treatment, as well as determining inheritance pattern and risks for family members.(1,2)
The risk for developing bleeding associated with these disorders and subtypes varies. The VWF and GP1BA genes have established bleeding risk and expert group guidelines.(1-4)
It is recommended that genetic testing be offered to all patients where it may assist in diagnosis and management of von Willebrand disease.(1) Genetic testing is integral to the conclusive diagnosis of platelet-type von Willebrand disease.(5)
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(6) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Method Description
Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the VWF and GP1BA genes, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp, and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the VWF and GP1BA genes.
There may be regions of the VWF and GP1BA genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences.(Unpublished Mayo method)
The reference transcript for VWF is NM_000552.4 and GP1BA is NM_000173.7. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.
Day(s) Performed
Varies
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
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
81408
81479
81479 (if appropriate for government payers)
88233-Tissue culture, skin, solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
88235-Amniotic fluid culture (if appropriate)
81265-Maternal cell contamination (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| GNVWD | VWF and GP1BA Genes, Full Gene NGS | 105337-0 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 619202 | Test Description | 62364-5 |
| 619203 | Specimen | 31208-2 |
| 619204 | Source | 31208-2 |
| 619205 | Result Summary | 50397-9 |
| 619206 | Result | 82939-0 |
| 619207 | Interpretation | 59465-5 |
| 619208 | Additional Results | 82939-0 |
| 619209 | Resources | 99622-3 |
| 619210 | Additional Information | 48767-8 |
| 619211 | Method | 85069-3 |
| 619212 | Genes Analyzed | 82939-0 |
| 619213 | Disclaimer | 62364-5 |
| 619214 | Released By | 18771-6 |