title: A new interference in some digoxin assays: anti-murine heterophilic antibodies.
abstract: BACKGROUND
  We describe a patient with cirrhotic liver disease and atrial fibrillation who was treated with spironolactone and digoxin. He was hospitalized because of an incidental finding of a high serum digoxin level (4.2 micrograms/L), but he remained asymptomatic without emerging arrhythmias. Despite discontinuation of both drugs, his serum digoxin level persisted at or above 3.0 micrograms/L for approximately 5 weeks, drawing into question the accuracy of the digoxin assay.
  
  
  METHODS
  Additional digoxin methods gave lower, discrepant results, providing evidence of an assay interference, and several possible sources of digoxin false positivity were evaluated. This included assessment of the contribution of digoxin-like immunoreactive factor (DLIF), digoxin metabolites, and spironolactone. Because the routine digoxin assay used a monoclonal antibody, we also tested for another hypothetical interference: human heterophilic ("anti-mouse") antibodies.
  
  
  RESULTS
  We found no contribution from DLIF, digoxin antibodies, or spironolactone to the apparent digoxin results. However, the use of protein A to complex and selectively remove immunoglobulin G molecules markedly lowered the apparent digoxin value, as did the less specific process of ultrafiltration.
  
  
  CONCLUSIONS
  These results suggest a previously unreported cause of digoxin false positivity: heterophilic antibodies, which have been reported to bind murine monoclonal antibodies in other assays. Because newer digoxin assays now use murine monoclonal antibodies, the possible presence of heterophilic, anti-mouse antibodies should now be considered in the interpretation of a high digoxin level.
authors.affiliation: Department of Medicine, Louisiana State University, School of Medicine, Shreveport, USA.
authors.forename: C
authors.initials: C
authors.lastname: Liendo
authors.forename: J K
authors.initials: JK
authors.lastname: Ghali
authors.forename: S W
authors.initials: SW
authors.lastname: Graves
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy*; D002298:Cardenolides; D004077:Digoxin / Q000097:blood* / Q000627:therapeutic use; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005189:False Positive Reactions; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012503:Saponins / Q000097:blood*; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D002298:Cardenolides; D004232:Diuretics; D012503:Saponins; C034504:digoxin-like factors; D013148:Spironolactone; D004077:Digoxin