Positive direct antiglobulin tests and immune hemolytic anemia in patients receiving procainamide.

To characterize the autoimmune phenomena in patients receiving procainamide, we studied the prevalence of positive direct antiglobulin (Coombs') tests and immune hemolytic anemia in 100 such patients and compared them with 100 age-matched and sex-matched controls. There was a significant increase in the frequency of positive direct antiglobulin tests in patients receiving procainamide (21 vs. 10 per cent, P = 0.05). The mechanism of red-cell sensitization in patients receiving procainamide was the production of red-cell autoantibody, which was serologically indistinguishable from that seen in warm autoimmune hemolytic anemia. In contrast, positive direct antiglobulin tests in control patients were due to the presence of complement components. Red-cell autoantibody production secondary to procainamide was not correlated with a higher-than-expected frequency of antinuclear antibodies or the clinical syndrome of drug-induced lupus erythematosus. In the series of 100 patients receiving procainamide, we identified three cases of immune hemolytic anemia. In two of the three cases, the anemia resolved after the medication was discontinued and did not require steroid therapy. We conclude that procainamide often results in the production of red-cell autoimmune phenomena.