Identify causal F8 variant in individuals with established mild to moderate hemophilia A and determine carrier status for those with a family history of mild to moderate hemophilia A. For severe hemophilia A, Hemophilia A (F8) 2 Inversions with Reflex to Sequencing and Reflex to Deletion/Duplication (2001614) is recommended.
- 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: Severe deficiency of factor VIII clotting activity leading to spontaneous joint or deep muscle bleeding. Moderate to mild deficiency is associated with prolonged bleeding after tooth extractions, surgery, or injuries and recurrent or delayed wound healing.
Incidence: 1 in 4,000-5,000 live male births worldwide, rare in females.
Inheritance: X-linked recessive. Of simplex cases, 85 percent of mothers are carriers and 10-15 percent of boys have a de novo mutation.
Penetrance: 100 percent in males and 10 percent in females.
Cause: Deleterious F8 gene mutations.
Clinical Sensitivity: 98 percent of mutations causing mild to moderate hemophilia A and 43 percent of severe hemophilia A mutations are detected by sequencing.
Methodology: Bidirectional sequencing of the entire F8 coding region and intron-exon boundaries.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations and gene duplications will not be detected in patients of either sex; large deletions will not be detected in females.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2001749||Hemophilia A (F8) Sequencing Interp|
|2001750||F8 FGS Specimen|
- Factor VIII
- Hemophilia A mild or moderate, molecular assay
- Hemophlia A sequencing assay