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Clinical Chemistry, Vol 31, 1525-1532, Copyright © 1985 by American Association for Clinical Chemistry
R Valdes Jr
Various laboratories have reported endogenous digoxin-like immunoreactive factor(s) (DLIF) in blood from patients in renal failure or liver failure, from newborn infants, and from third-trimester pregnant women. Similar immunoreactivity has been detected in amniotic fluid, in cord blood, and in urine and serum from normal subjects. The factor(s) giving rise to this immunoreactivity cross react with antibodies used in many currently available immunoassays for digoxin, sometimes causing apparent digoxin concentrations exceeding the therapeutic range obtained for exogenous digoxin, with consequent errors in measurement and in subsequent clinical interpretation of digoxin results. Here, I summarize findings in our laboratory and those of others. DLIF evidently exist in three states in serum: tightly protein-bound, weakly protein-bound, and unbound (free). In normal subjects, greater than 90% of the total DLIF in serum is tightly but reversibly bound to serum proteins and is not readily detectable by direct measurement of digoxin in serum with conventional immunoassays. However, there seems to be a redistribution of the more weakly bound and unbound components in patients with renal failure, pregnant women, and newborns. The increased values detected in these groups are ascribable to increased amounts of weakly bound and unbound DLIF rather than to increased total DLIF. Carrier proteins may play a prominent role in the transport of these factors in blood. I discuss the potential physiological and pharmacological implications of detecting endogenous immunoreactive factors that cross react with antibodies to drugs.
The following articles in journals at HighWire Press have cited this article:
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  M. R. Litonjua, S. Penton, C. Robinson, and G. P. Daubert Digoxin: The Monarch of Cardiac Toxicities Journal of Pharmacy Practice, June 1, 2005; 18(3): 157 - 168. [Abstract] [PDF]
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 H. M. A. M. Qazzaz, M. A. El-Masri, and R. Valdes Jr. Secretion of a Lactone-Hydrogenated Ouabain-Like Effector of Sodium, Potassium-Adenosine Triphosphatase Activity by Adrenal Cells Endocrinology, September 1, 2000; 141(9): 3200 - 3209. [Abstract] [Full Text] [PDF]
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 E. Schutz, M. Shipkova, P. D. Niedmann, E. Wieland, V. W. Armstrong, and M. Oellerich Determination of monoethylglycinexylidide by fluorescence polarization immunoassay in highly icteric serum samples: modified precipitation procedure and HPLC compared Clin. Chem., June 1, 1998; 44(6): 1269 - 1274. [Abstract] [Full Text] [PDF]
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B. A. Way, T. R. Wilhite, R. Miller, C. H. Smith, and M. Landt Vitros Digoxin Immunoassay Evaluated for Interference by Digoxin-like Immunoreactive Factors Clin. Chem., June 1, 1998; 44(6): 1339 - 1340. [Full Text] [PDF]
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H. M. E. Azzazy, S.-H. Duh, A. Maturen, E. Schaller, L. Shaw, R. Grimaldi, G. Shock, and R. H. Christenson Multicenter study of Abbott AxSYM(R) Digoxin II assay and comparison with 6 methods for susceptibility to digoxin-like immunoreactive factors Clin. Chem., September 1, 1997; 43(9): 1635 - 1640. [Abstract] [Full Text] [PDF]
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A. Scholer, J. Boecker, U. Engelmayer, K. Feldmann, D. Hannak, R. Kattermann, M. Oellerich, H. Raith, H. Schlebusch, H. Wieland, et al. Comparability of a new turbidimetric digoxin test with other immunochemical tests and with HPLC—a multicenter evaluation Clin. Chem., January 1, 1997; 43(1): 92 - 99. [Abstract] [Full Text] [PDF]
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 H. M. A. M. Qazzaz, S. L. Goudy, and R. Valdes Jr. Deglycosylated Products of Endogenous Digoxin-like Immunoreactive Factor in Mammalian Tissue J. Biol. Chem., April 12, 1996; 271(15): 8731 - 8737. [Abstract] [Full Text] [PDF]
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