A 44 year old male was diagnosed as suffering from drug-induced immune hemolytic anemia due to midecamycin, a macrolide antibiotic. He received this antibiotic for 3 days (total 1,200 mg) 3 weeks preceding the onset of massive intravascular hemolysis. On admission severe anemia with reticulocytopenia, jaundice, hepatosplenomegaly, marked elevation of serum lactic dehydrogenase, and undetectable haptoglobin were noted. His serum was dark-brown in color. Gross hematuria, hemoglobinuria and hemosiderinuria as well as mild azotemia were also present. Antiglobulin test was negative.
Immunological investigations were undertaken to identify the causative agent and to elucidate pathogenetic mechanism. Patient's RBCs which were obtained after subsidence of hemolysis were incubated with several possibly causative drugs including midecamycin, cephalexin, cephalotin, sulpyrine and aminopyrin. RBCs were then washed extensively with saline before they were mixed with his own sera obtained during the period of active hemolysis. Agglutination was positive only with midecamycin-treated RBCs at 25°C but negative at 4°C. The indirect antiglobulin test was performed on his serum as follows: Midecamycin-treated patient's RBCs were incubated with his serum before washing, and they were then allowed to react with the added monospecific antiglobulin sera. Positive agglutination was observed only with anti-IgM globulin suggesting the antibody class being IgM. Agglutination was positive up to 8 times dilution of serum. However, the haptenic inhibition was not demonstrated under the experimental conditions employed.
These results suggest that generation of IgM antibody directed against midecamycin was responsible for the occurrence of hemolysis in this patient. The hapten-cell mechanism was likely to have played the major role in the pathogenesis, though participation of the innocent bystander mechanism was not completely ruled out.
