Test Catalog

Test Id : F11NG

Hemophilia C, F11 Gene, Next-Generation Sequencing, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Genetic confirmation of a factor XI deficiency diagnosis with the identification of known or suspected pathogenic alterations in the F11 gene

 

Carrier testing for close family members of an individual with a factor XI deficiency diagnosis

 

This test is not intended for prenatal diagnosis

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Genetic testing for factor XI deficiency should only be considered after coagulation screening is performed and if factor XI activity is less than 50% of normal (note: reference ranges may vary depending on the locally established reference range).

 

Genetic testing for factor XI deficiency is indicated if:

-Factor XI activity is reduced (less than 50% of normal)

-Acquired causes of factor XI have been excluded

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Custom Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing when appropriate

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

F11 Gene, Full Gene NGS

Aliases
Lists additional common names for a test, as an aid in searching

Hemophilia C

Factor XI deficiency

Plasma thromboplastin antecedent deficiency

PTA

Rosenthal syndrome

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Genetic testing for factor XI deficiency should only be considered after coagulation screening is performed and if factor XI activity is less than 50% of normal (note: reference ranges may vary depending on the locally established reference range).

 

Genetic testing for factor XI deficiency is indicated if:

-Factor XI activity is reduced (less than 50% of normal)

-Acquired causes of factor XI have been excluded

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

The clinical workup for factor XI deficiency begins with special coagulation testing for factor XI. Order F_11 / Coagulation Factor XI Activity Assay, Plasma.

Shipping Instructions

Ambient and refrigerated specimens must arrive within 7 days (168 hours of draw), and frozen specimens must arrive within 14 days (336 hours of draw).

Collect and package specimen as close to shipping time as possible.

Necessary Information

Rare Coagulation Disorder 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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD) or light-blue top (3.2% sodium citrate)

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: Ambient (preferred)/Refrigerated/Frozen

 

Specimen Type: Extracted DNA

Container/Tube: 1.5- to 2-mL tube

Specimen Volume: Entire specimen

Collection Instructions:

1. Label specimen as extracted DNA and source of specimen.

2. Provide indication of volume and concentration of the DNA.

Specimen Stability: Frozen (preferred)/Refrigerated/Ambient

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. 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)

2. If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL

Extracted DNA: 100 mcL at 50 ng/mcL concentration

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Ambient (preferred) 7 days
Frozen 14 days
Refrigerated 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Genetic confirmation of a factor XI deficiency diagnosis with the identification of known or suspected pathogenic alterations in the F11 gene

 

Carrier testing for close family members of an individual with a factor XI deficiency diagnosis

 

This test is not intended for prenatal diagnosis

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Genetic testing for factor XI deficiency should only be considered after coagulation screening is performed and if factor XI activity is less than 50% of normal (note: reference ranges may vary depending on the locally established reference range).

 

Genetic testing for factor XI deficiency is indicated if:

-Factor XI activity is reduced (less than 50% of normal)

-Acquired causes of factor XI have been excluded

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Factor XI deficiency (FXID) is a bleeding diathesis that is also known as hemophilia C. FXID produces a bleeding disorder that is relatively mild, rarely spontaneous, and associated with certain sites of the body, namely the oral cavity, nasopharynx, and urinary tract. Bleeding frequency and severity are highest when trauma or certain surgical procedures involve tissues in these areas. Menorrhagia and nose bleeds are common.

 

Overall, in the general population, the prevalence of severe FXID is 1 per million. However, FXID is common in certain ethnic groups. In Ashkenazi Jews, severe deficiency is found in 1 in 450 people. Founder mutations are also found among French Basques and French individuals from Nantes. Hereditary FXID is typically inherited in an autosomal recessive manner. However, some rare alterations exert a dominant-negative effect or interfere with the functioning of normal factor XI (FXI), causing an autosomal dominant bleeding disorder.

 

FXID is a result of defects in the concentration or function of coagulation FXI, which is synthesized in the liver and circulates in blood plasma as an inactive zymogen. The role of activated FXI includes sustained activation of factor IX, leading to fibrin formation and clot stability, especially in tissues with high fibrinolytic activity, such as oral cavity, nasopharynx, and urinary tract. A significant deficiency in the amount of functional FXI can cause excessive bleeding in these tissues after trauma or certain surgical procedures.

 

FXID is defined as severe when FXI activity is less than 15% (15 U/dL). It is considered moderate when it is between 15% and 50% (15 to 50 U/dL). However, plasma FXI activity levels to do not correlate well with bleeding phenotype, in part activity levels appear unable to reflect true physiological activity of FXI (eg, p.Ser266Asn is associated with bleeding and defective FXI binding to platelets but is reported not affect aPTT). Some patients with 15% to 50% FXI activity present similarly to severely deficient patients, indicating contributing factors to disease severity, eg, the qualities of the specific alteration(s) underlying the disorder or the co-inheritance of other bleeding disorders. Of note, normal, full-term newborn infants or healthy premature infants may have decreased levels (greater than or equal to 10%) that may not reach adult levels for greater than or equal to 180 days after birth.

 

The F11 gene encodes FXI. Genetic testing for pathogenic alterations in F11 is indicated if FXI activity is below 50% of normal. Patients lacking FXI will also typically have very long activated partial thromboplastin times.

 

Acquired FXID appears to be a rare complication of liver disease. Liver disease should be excluded prior to genetic testing.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

 

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Consultations with the Mayo Clinic Special Coagulation Clinic, Molecular Hematopathology Laboratory, or Thrombophilia Center are available for DNA diagnosis cases. This may be especially helpful in complex cases or in situations where the diagnosis is atypical or uncertain.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical:

Some individuals may have a variant that is not identified by the methods performed. The absence of a variant, therefore, does not eliminate the possibility of factor XI deficiency. This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies significantly lower than 50%. Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Technical Limitations:

Next-generation sequencing (NGS) may not detect all types of genetic variants. Additionally, rare variants (ie, polymorphisms) may be present that could lead to false-negative or false-positive results. Therefore, test results should be interpreted in the context of activity and antigen measurements, clinical findings, family history, and other laboratory data. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If multiple alterations are identified, NGS is not able to distinguish between alterations that are found in the same allele ("in cis") and alterations found on different alleles ("in trans"). This limitation may complicate diagnosis or classification and has implications for inheritance and genetic counseling. To resolve these cases, molecular results must be correlated with clinical history, activity and antigen measurements, and family studies.

 

Unless reported or predicted to cause disease, alterations found deep in the intron or alterations that do not result in an amino acid substitution are not reported. These and common alterations (ie, polymorphisms) identified for this patient are available upon request.

 

Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Palla R, Peyvandi F, Shapiro AD: Rare bleeding disorders: diagnosis and treatment. Blood. 2015 Mar;125(13):2052-2061

2. Wheeler A, Gailani D: Why factor XI deficiency is a clinical concern. Expert Review of Hematology. 2016 Jul;9(7):629-637

3. Bolton-Maggs, P: Factor XI deficiency-resolving the enigma? Hematology Am Soc Hematol Educ Program. 2009;97-105

4. Emsley J, McEwan PA, Gailani D: Structure and function of factor XI. Blood. 2010 Apr;115(13):2569-2577

5. Gailani D, Geng Y, Verhamme I, et al: The mechanism underlying activation of factor IX by factor XIa. Thromb Res. 2014 May;133 Suppl 1:S48-51

6. Berber E: Molecular characterization of FXI deficiency. Clin Appl Thromb Hemost. 2011 Feb;17(1):27-32

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing (NGS) and/or Sanger sequencing are performed.

 

Regions of homology, high guanine-cytosine (GC)-rich content, and repetitive sequences may not provide accurate sequence. Therefore, all reported alterations detected by NGS in these regions are confirmed by an independent reference method. However, this does not rule out the possibility of a false-negative result in these regions.

 

Sanger sequencing is used to confirm alterations detected by NGS when appropriate.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

21 to 28 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks; DNA: Indefinitely

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81479

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports