Molecular testing to confirm a phenotypic diagnosis of von Willebrand disease type 2A.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA) or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Mucocutaneous bleeding after brushing or flossing teeth, unexplained bruising, prolonged repeated nosebleeds, menorrhagia, and prolonged bleeding following childbirth, trauma or surgery.
Incidence: Approximately 1 in 100 to 1 in 1000 individuals.
Inheritance: Autosomal dominant for types 2B, 2M and most of 2A; autosomal recessive for 20 percent of 2A.
Penetrance: Dominant mutations are incompletely penetrant when VWF: Ag and VWF: RCo levels are 25-50 IU/dL. Full penetrance is expected when VWF: Ag and VWF: RCo levels are less than 25 IU/dL.
Cause: Pathogenic VWF mutations.
Clinical Sensitivity: 99 percent for vWD type 2A and 80 percent for types 2B and 2M; unknown for other vWD subtypes.
Methodology: Bidirectional sequencing of VWF exon 28 and its intron-exon boundaries; if no pathogenic mutations are detected, bidirectional sequencing of exons 11, 12, 14, 15, 16, 24, 25, 51, and 52 and the corresponding intron-exon boundaries is performed.
Analytical Sensitivity and Specificity: 99 percent.
Limitations:Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletion/duplications will not be detected. Mutations lying outside of VWF exons 11, 12, 14, 15, 16, 24, 25, 28, 51 and 52 are not evaluated.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2005481||vWD Type 2A (VWF) Sequencing Specimen|
|2005482||vWD Type 2A (VWF) Sequencing Interp|
- VWD platelet type 2A reflex
- VWF2A Sequencing