Two types of nomifensine-induced immune haemolytic anaemias: drug-dependent sensitization and/or autoimmunization

Thirty-one patients who developed immune haemolytic anaemia while receiving nomifensine were studied. We provide evidence that nomifensine can cause two forms of immune haemolytic anaemia: one that is associated with an abrupt haemolytic episode due to drug-dependent antibodies, and a less acute form associated with IgG autoantibodies. The majority of patients' serum samples (23 cases) contained IgG and/or IgM antibodies reacting to a highly variable extent with red blood cells (RBC) only in the presence of the drug and/or its metabolites. Sera of six patients contained IgG autoantibodies which reacted, like those in warm autoimmune haemolytic anaemia, with RBC in the absence of drugs. Three patients had developed both types of antibodies. From a diagnostic viewpoint, nine of the drug-dependent antibodies could not be identified by using the drug itself, but by its known (three cases) or unknown urine-born metabolites (ex vivo antigens). We conclude that nomifensine can induce in vivo the production of RBC drug- and/or metabolite-dependent antibodies, autoantibodies, or both in the same patient.