A NEW INTERFERENCE IN SOME DIGOXIN ASSAYS - ANTIMURINE HETEROPHILIC ANTIBODIES

Background: We describe a patient with cirrhotic Liver disease and atr ial fibrillation who was treated with spironolactone and digoxin. He w as hospitalized because of an incidental finding of a high serum digox in level (4.2 mu g/L), but he remained asymptomatic without emerging a rrhythmias. Despite discontinuation of both drugs, his serum digoxin l evel persisted at or above 3.0 mu g/L for similar to 5 weeks, drawing into question the accuracy of the digoxin assay.Methods: Additional di goxin methods gave lower, discrepant results, providing evidence of an assay interference, and several possible sources of digoxin false pos itivity were evaluated. This included assessment of the contribution o f digoxin-like immunoreactive factor (DLIF), digoxin metabolites, and spironolactone. Because the routine digoxin assay used a monoclonal an tibody, we also tested for another hypothetical interference: human he terophilic (''anti-mouse'') antibodies. Results: We found no contribut ion from DLIF, digoxin antibodies, or spironolactone to the apparent d igoxin results. However, the use of protein A to complex and selective ly remove immunoglobulin G molecules markedly lowered the apparent dig oxin value, as did the less specific process of ultrafiltration. Concl usions: These results suggest a previously unreported cause of digoxin false positivity: heterophilic antibodies, which have been reported t o bind murine monoclonal antibodies in other assays. Because newer dig oxin assays now use murine monoclonal antibodies, the possible presenc e of heterophilic, anti-mouse antibodies should now be considered in t he interpretation of a high digoxin level.