Ordering Recommendation

Identify causal F8 gene intron 22A or intron 1 variant in individuals with established severe hemophilia A and determine carrier status of those with relatives with a known inversion of intron 1 or 22A. The most comprehensive test for individuals with severe hemophilia A is Hemophilia A (F8) 2 Inversions with Reflex to Sequencing and Reflex to Deletion/Duplication​ (2001614). For mild to moderate hemophilia A, Hemophilia A (F8) Sequencing (2001747) is recommended.

Mnemonic
F8 INV
Methodology

Inverse Polymerase Chain Reaction/Electrophoresis

Performed

Varies

Reported

Within 14 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval
Interpretive Data

Background Information for Hemophilia A (F8) 2 Inversions:
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: 51 percent of mutations causing severe hemophilia A are detected by F8 inversion testing. This assay does not detect F8 mutations associated with mild or moderate hemophilia A in males.
Methodology: Intron 22-A and intron 1 inversions detected by inverse PCR and electrophoresis.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. F8 mutations, other than the F8 intron 22-A and intron 1 inversions, will not be detected.

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
Hotline History
N/A
Components
Component Test Code* Component Chart Name LOINC
2001761 Hemophilia A (F8) Inversions Interp 82343-5
2001762 F8 Inv Specimen
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Aliases
  • DNA Analysis for Hemophilia A
  • F8
  • Carrier Detection and Prenatal Diagnosis
  • Carrier Detection of Hemophilia A
  • F8 Inversion
  • Factor VIII Deficiency
  • Factor VIII Inversion
  • Factor VIII Inversions
  • Hemophilia A
  • Hemophilia A (Factor VIII) Inversions
  • Severe Hemophilia A
Hemophilia A (F8) 2 Inversions