Test Catalog

Diagnosis of congenital coagulopathies by NGS: von Willebrand Disease

Code: LRD2833

Type: Estudi de coagulopaties congènites

Clinical information

Diagnostic Utility:

Identifying the molecular defect in VWF in patients diagnosed with VWD.

Von Willebrand Disease (VWD)

VWD is the most common inherited bleeding disorder in the population with an estimated prevalence between 0.01-1%, and is caused by quantitative or qualitative deficits in von Willebrand factor (VWF). Depending on the type of deficit, three main categories are distinguished: type 1 VWD characterized by a partial reduction in VWF levels, type 3 VWD due to a total absence of the factor, and type 2 VWD due to qualitative defects. Depending on the altered function, 4 different subtypes are distinguished: 2A, 2B, 2M, and 2N. The most common symptoms observed in these patients are mucocutaneous bleeding and those arising from compromising the hemostatic system, such as those derived from surgeries or dental extractions, although bleeding in the central nervous system or gastrointestinal tract has also been described in more severe cases. In women, menorrhagia is the most frequent symptom.

Most types of VWD are inherited in an autosomal dominant manner, except for type 3 VWD and type 2N VWD, which are inherited in an autosomal recessive manner. This bleeding disorder is caused by mutations in the gene that encodes for VWF. Currently, more than 700 genetic alterations in VWF have been identified that lead to this condition. When the VWF protein is altered, platelets cannot aggregate and adhere properly to blood vessels when a lesion occurs. As a result, the coagulation process is affected, leading to bleeding.

Application of a multi-gene panel based on the simultaneous amplification of exons and flanking intronic regions for their sequencing using next-generation sequencing (NGS) techniques allows for the simultaneous molecular study of genes related to congenital coagulopathies and inherited bleeding disorders, including the von Willebrand factor (VWF).

Method:

Next-generation sequencing (NGS)

Massive sequencing of the exons and flanking intronic regions of VWF using a panel of genes related to congenital coagulopathies.

Traditional Sanger sequencing to confirm the detected mutation(s) in patients diagnosed with VWD, in order to reach an unequivocal result by analysing the specific region where the variant is located.

If no potential or definitively causative mutation is identified, it will be reported and discussed with the requesting medical team the possibility of conducting complementary studies.

Reference Values

Not applicable

Diagnostic Algorithm:

Not applicable

Turnaround Time:

20 working days

Specimen information

Sample: Whole blood
Tube: EDTA K3 tube, 5-10 ml if it is a blood sample
Minimum essential volume: 3 ml

Stability:

  • At room temperature: 4 days
  • In refrigeration: 10 days

Transport instructions: Preferably at room temperature

Reason for rejection: Coagulated sample and/or incorrectly identified.

Other accepted sample types:

  • Purified DNA, minimum 300 ng (30 ng/µL)
  • Buccal mucosa: contact the laboratory to consult sample collection specifications.

Administrative information

BST Code: LRD2833
Test Description: Molecular diagnosis of congenital coagulopathies by NGS: von Willebrand disease.
Synonyms: Genetic study of VWD, molecular study of von Willebrand disease, VWF sequencing.
Section: Congenital Coagulopathies
BST Fee: Check the updated fees here.

The box VWD must be checked on the molecular study request form, and the available phenotypic data must be filled in.

Profiles:

N/A.

References

  • Peter J Hulick. Next-generation DNA sequencing (NGS): Principles and clinical Applications. Waltham, MA: UpToDate Inc. https://www.uptodate.com
  • DNA Sequencing by Capillary Electrophoresis. Applied Biosystems Chemistry Guide. Second Edition.

Base de dades de mutacions