FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 313:469-474 August 22, 1985 Number 8 Next

	Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Abstract

Nomifensine is an antidepressant drug (widely used in Europe, but not yet available in the United States), which has been linked to intravascular hemolysis. We studied 19 patients (18 women and 1 man) with acute intravascular hemolysis due to nomifensine-dependent antibodies. Transitory renal insufficiency developed in at least seven patients, and four required temporary dialysis. To investigate the antibodies, we used nomifensine, its three main metabolites, and its ex vivo antigens (urine samples from a volunteer collected 1.5 to 16 hours after the ingestion of 100 mg of nomifensine). We found an extraordinary heterogeneity of antibody response. Only five antibodies appeared to be primarily reactive with nomifensine. The remaining antibodies reacted either optimally or exclusively in the presence of one or more of the metabolites. Three of the metabolite-specific antibodies were positive only in the presence of ex vivo antigens, indicating specificity for as-yet-unidentified early and late metabolites of nomifensine. All the antibodies were capable of activating complement and belonged to the IgG or IgM class or both. Two serum samples also contained weak IgA antibodies. In addition to a variable degree of cross-reactivity of the antibodies, at least one serum sample had two drug-dependent red-cell antibodies (IgG against nomifensine and IgM against metabolites), and one sample had a drug-dependent IgM red-cell antibody and an IgG platelet antibody. Despite their serologic heterogeneity, all the antibodies were strongly reactive with ex vivo antigens. We recommend the use of ex vivo antigens as the technique of choice for the detection of nomifensine-dependent (and probably other drug-dependent) antibodies.

This article has been cited by other articles:

• Bougie, D. W., Benito, A. I., Sanchez-Abarca, L. I., Torres, R., Birenbaum, J., Aster, R. H. (2007). Acute thrombocytopenia caused by sensitivity to the glucuronide conjugate of acetaminophen. Blood 109: 3608-3609 [Full Text]  
• Obach, R. S., Dalvie, D. K. (2006). METABOLISM OF NOMIFENSINE TO A DIHYDROISOQUINOLINIUM ION METABOLITE BY HUMAN MYELOPEROXIDASE, HEMOGLOBIN, MONOAMINE OXIDASE A, AND CYTOCHROME P450 ENZYMES. Drug Metab. Dispos. 34: 1310-1316 [Abstract] [Full Text]  
• Bougie, D., Aster, R. (2001). Immune thrombocytopenia resulting from sensitivity to metabolites of naproxen and acetaminophen. Blood 97: 3846-3850 [Abstract] [Full Text]