Test Catalog

Test Id : FRDIG

Digoxin, Free, Serum

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

Evaluating recrudescent (breakthrough) digoxin toxicity in renal-failure patients

 

Assessing the need for more antidigoxin Fab to be administered

 

Deciding when to reintroduce digoxin therapy

 

Monitoring patients with possible digoxin-like immunoreactive factors (DLIFs)

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

Ultrafiltration followed by Electrochemiluminescent Immunoassay

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

Digoxin, Free, S

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: For 12 hours before specimen collection do not take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Container/Tube: 

Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 1 mL

Collection Instructions:

1. Draw blood 6 to 8 hours after last dose of digoxin.

2. Serum gel tubes should be centrifuged within 2 hours of collection.

3. Red-top tubes should be centrifuged, and the serum aliquoted within 2 hours of collection.

Forms

If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Cardiovascular Test Request Form (T724)

-Therapeutics Test Request (T831)

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

0.6 mL

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

Gross hemolysis Reject

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
Serum Refrigerated (preferred) 7 days
Frozen 180 days

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

Evaluating recrudescent (breakthrough) digoxin toxicity in renal-failure patients

 

Assessing the need for more antidigoxin Fab to be administered

 

Deciding when to reintroduce digoxin therapy

 

Monitoring patients with possible digoxin-like immunoreactive factors (DLIFs)

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

Digoxin, a widely prescribed cardiac drug, has a narrow therapeutic window (a very small difference exists between therapeutic and toxic tissue concentrations). While excess digoxin can have serious side effects (eg, cardiac dysrhythmias, heart failure, seizures, death), it is one of the few therapeutic drugs for which antidotal therapy is available.(1) In toxic situations, antibody fragment therapy, which involves the administration of antibodies to digoxin (eg, Digibind, Digoxin Immune Fab), is indicated. In manufacturing of Digibind, papain cleaves digoxin-specific IgG antibody into 2 antigen binding-site fragments (Fab fragments). These fragments bind to digoxin, block the active site of the digoxin molecule, and make it unavailable to its receptor molecule and biologically inactive. The Fab fragment-digoxin complex is then excreted by the kidney.

 

Total digoxin concentration in blood increases approximately 10 to 30 fold after administration of Fab fragments. On the other hand, the unbound (free) fraction, which is responsible for its pharmacological activity, decreases. Traditional digoxin assays performed by immunoassay (eg, DIG / Digoxin, Serum) measure both Fab fragment-bound (inactive) digoxin and free (active) digoxin (ie, total digoxin), and are unsuitable for managing patients when digoxin-specific Fab fragment therapy has been administered. Assays for measurement of free digoxin levels only are necessary in such situations.

 

The kidneys provide the main route of Fab fragment elimination from the body. In patients with normal renal function, digoxin-specific Fab fragments are excreted in the urine with a biological half-life of 15 to 20 hours. Ordinarily, improvement in signs or symptoms of digoxin intoxication begins within a half hour or less after initiation of Fab fragment therapy. Clearance may be delayed in patients with renal failure. In such patients, toxicity may recur if previously bound drug is released from the Fab fragments, resulting in increased levels of free digoxin.

 

Digoxin-like immunoreactive factors (DLIFs) are endogenous substances that can cross-react with testing antibodies used in some digoxin immunoassays, causing erroneous results. DLIFs may be seen in certain volume-expanded patients such as neonates, patients with renal or liver disease, and in women in the third trimester of pregnancy being treated with digoxin.(2) DLIFs are strongly bound to proteins and, in this assay, are removed prior to testing.

 

The following ordering guidelines are offered:

-When creatinine clearance is less than 30 mL/min/surface area: order free digoxin levels daily for 12 days (or until dismissal)

-When creatinine clearance is equal to or above 30 mL/min/surface area (and the patient is not on renal-replacement therapy): order free levels daily for 72 hours, as long as the last level is not supratherapeutic (these patients are expected to have good clearance and a lower risk for reintoxication)

-Also order total digoxin levels every other day during the time periods above, with a goal of determining whether there is correlation between changes in free and total levels.

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.

<16 years:

Therapeutic ranges have not been established for patients who are under 16 years of age. In adults, the suggested serum free digoxin therapeutic range is 0.4-0.9 ng/mL.

Toxic concentration: > or =3.0

 

> or =16 years:

0.4-0.9 ng/mL   

Toxic concentration: > or =3.0 ng/ mL

Interpretation
Provides information to assist in interpretation of the test results

The target therapeutic level is 0.4 to 0.9 ng/mL. Toxicity may be seen when free digoxin concentrations are 3.0 ng/mL or higher. Pediatric patients may tolerate higher concentrations.

 

Therapeutic concentrations for free digoxin are 25% lower than therapeutic values for total digoxin due to the separation of protein-bound digoxin in the assay.

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

Patients vary in their responsiveness to digoxin.

 

Renal dysfunction alters the metabolism of digoxin and antibody-bound digoxin.

 

It takes 6 to 8 hours after digoxin administration for equilibration between serum and tissue; results obtained from specimens collected less than 6 to 8 hours after the last dose of digoxin should be interpreted with caution.

 

Digibind (Glaxo Wellcome, Research Triangle Park, NC) is the most common brand of antidigoxin Fab fragments used; other brands are available and may be monitored by this assay.

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

1. Jortani SA, Pinar A, Johnson NA, Valdes R Jr: Validity of unbound digoxin measurements by immunoassays in presence of antidote (Digibind). Clin Chim Acta. 1999;283:159-169

2. DIGIBIND Digoxin Immune FAB (Ovine). Package insert. GlaxoSmithKline; 2003

3. Moyer TP, Boeckx RL, eds: Applied Therapeutic Drug Monitoring. Vol 2. American Association for Clinical Chemistry Press; 1984

4. Jortani SA, Voldes R Jr: Digoxin and its related endogenous factors. Crit Rev Clin Lab Sci. 1997;34:225-274

5. Datta P, Hinz V, Klee G: Comparison four digoxin immunoassays with respect to interference from digoxin-like immunoreactive factors. Clin Biochem. 1996;29(6):541-547

6. Soldin SJ: Free drug measurements. When and why? An overview. Arch Pathol Lab Med. 1999;123:822-823

7. Dickstein K, Cohen-Solal A, Filippatos G, et al: ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Eur Heart J. 2008;29:2388-2442

8. Milone MC, Shaw LM: Therapeutic drugs and their management. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics 6th ed. Elsevier; 2018800-831

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

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.

Monday through Sunday

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.

Same day/1 day

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

7 days

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 has been modified from the manufacturer's instructions. Its performance characteristics were 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.

80163

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