Test ID: FRDIG
Digoxin, Free, Serum
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Specimen Volume: 1 mL
Collection Instructions: Draw blood 6 to 8 hours after last dose of digoxin.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Refrigerated (preferred) | 7 days |
| Frozen | 180 days |
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/8674 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 that only measure free digoxin levels 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 <30 mL/min/surface area: order free digoxin levels daily for 12 days (or until dismissal)
-When creatinine clearance is > or =30 mL/min/surface area (and patient is not on renal-replacement therapy): order free levels daily for 72 hours, as long as 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.
Therapeutic concentration: 0.4-1.5 ng/mL
Toxic concentration: > or =3.0 ng/mL
Pediatric toxic concentrations may be higher.
Interpretation Provides information to assist in interpretation of the test results
The target therapeutic is 0.4 ng/mL to 1.5 ng/mL. Toxicity may be seen when free digoxin concentrations are > or =3.0 ng/mL. 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 <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 Provides recommendations for further in-depth reading of a clinical nature
1. Saeed JA, Pinar A, Johnson NA: Validity of unbound digoxin measurements by immunoassays in presence of antidote (Digibind) Clinical Chemistry 1999;283:159-169
2. Package insert: DIGIBIND Digoxin Immune FAB (Ovine). GlaxoSmithKline, Research Triangle Park NC, 2003
3. Applied Therapeutic Drug Monitoring. Vol 2. Edited by TP Moyer, RL Boeckx. Washington, DC, American Association for Clinical Chemistry, 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, Steven. Free Drug Measurements When and Why? An Overview. Arch Pathol Lab Me 1999;123:822-823
Method Description Describes how the test is performed and provides a method-specific reference
Free digoxin not bound to the digoxin-specific antibody fragments and not bound to protein is separated from bound digoxin by a 30-kD centrifugal filter device. Free digoxin passes through the filter; bound digoxin is retained in the filter. The filtrate is analyzed for digoxin using the E170 Digoxin method, a competitive electrochemiluminescence immunoassay that employs a monoclonal antibody directed against digoxin. Digoxin in the specimen competes with the added digoxin derivative labeled with biotin for the binding sites on the ruthenylated antibody-complex. Streptavidin-coated microparticles are added and the mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Application of voltage to the electrode induces the chemiluminescent emission, which is then measured.(Package insert: Roche Digoxin, 2005)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Sunday; Continuously
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
80162
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| FRDIG | Digoxin, Free, S | 3562-6 |
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