Free Digoxin

Performed in Chemistry at BUMCP

DIGF

Green LiHep, Plasma

Gold/SST, Red

Samples must be centrifuged within one hour of collection and must be removed from gel separator or cells within 4 hours.

Refrigerated - 2 days
Frozen - 6 months

Collected in an outdated/expired tube
Hemolyzed, icteric or lipemic
Contaminated

Daily, Sunday through Saturday

Less than 4 hours

Digoxin, a widely prescribed cardiac drug, has a narrow therapeutic window. 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. In toxic situations, antibody fragment therapy, which involves the administration of antibodies to digoxin (eg, Digibind, Digoxin Immune Fab), is indicated. 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 (i.e., DIG / Digoxin, Serum) measure both Fab fragment-bound (inactive) digoxin and free (active) digoxin (i.e., 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. DLIFs are strongly bound to proteins and, in this assay, are removed prior to testing.  The Elecsys Digoxin assay employs a competitive test principle using a monoclonal antibody specifically directed against digoxin. Digoxin in the sample competes with the added digoxin derivative labeled with biotin for the binding sites on the ruthenylated antibody-complexa ). a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy)2 3 + ))