Acta haemat. 55: 109-117 (1976)
Cephalothin-Induced Immune Hemolytic Anemia M. J eannet, A. B loch, J. M. D ayer, J. J. F arquet, J. P. G irard and A. C ruchaud Department of Medicine, Hôpital cantonal, Geneva
Key words. Cephalothin Immune reactions
Drug-induced hemolytic anemia • Hemolytic anemia •
Abstract. A patient with renal disease developed Coombs-positive hemolytic ane mia while receiving cephalothin therapy. An anti-cephalothin IgG antibody was de tected in the patient’s serum and in the eluates from her erythrocytes. In addition, nonimmunologic binding of normal and patient’s serum proteins to her own and cephalothin-coated normal red cells was demonstrated. Skin tests and in vitro lym phocyte stimulation revealed that the patient was sensitized to cephalothin and also to ampicillin. Careful investigation of drug-induced hemolytic anemias reveals the complexity of the immune mechanisms involved.
Downloaded by: UCL 144.82.238.225 - 5/7/2018 7:03:47 PM
Drug-induced immune hemolytic anemias are uncommun despite the fact that many drugs lead to the development of antibodies. However, some of these drugs, such as penicillin, bind firmly to red cells in vitro and more than 20 cases of penicillin-induced hemolytic anemia have been re ported [11]. Cephalothin and other cephalosporins which are chemically related to penicillin, also bind to red cells in vitro. Cephalothin sodium (Keflin) has been associated with a positive direct Coombs test in many patients receiving this antibiotic [4, 7] but only 2 cases of cephalothin and 1 case of cephalexin-induced immune hemolytic anemia have been re ported as yet [2, 5]. The purpose of this paper is to report an additional case of Coombs-positive hemolytic anemia related to cephalothin therapy and to define the characteristics of immunohematologic reactions to this drug.
110
J eannet/B loch/D ayer/F arquet/G irard/C ruchaud
Case Report A 61-year-old woman was admitted to the Hopital cantonal, Geneva, on June 3, 1970, because of weakness, nausea, vomiting and weight loss. Bilateral renal stones with chronic pyelonephritis and progressive renal failure had been diagnosed several years earlier. Physical examination was unremarkable, but laboratory investigations revealed an urinary infection and a severe renal failure with a blood urea nitrogen level of 77 mg/100 ml, a creatinine value of 6.2 mg/100 ml and a creatinine clear ance of 4 ml/min. Hyperparathyroidism was diagnosed and on July 3, 1970, parathyroidectomy was performed. The postoperative course was stormy with several episodes of re spiratory arrest requiring intubation and artificial ventilation, bronchopneumonia, cardiac arythmia, and acute pulmonary edema. From June 13 to July 12, 1970, the patient was treated with 500 mg ampicillin every 6 h; then from July 13 to July 28, 1970, 200 mg gentamycin were administered in 5 doses. From July 15, 1970 the pa tient was treated with cephalothin sodium, 4 g/day for 23 days. Before receiving cephalothin, the patient’s hematocrit level was 30%, the reticulocyte count was 1.3% and the Coombs test was negative. On August 4, 1970 after 21 days of cephalothin therapy, the hematocrit was 18.5% and hemoblogin 5.5 g/100 ml. Ten days later, the reticulocyte count was 16%. A direct Coombs test was positive using a standard an ti-whole serum and a specific anti-IgG reagent (table I). The serum complement was normal. Cephalothin therapy was discontinued on August 6, 1970, but a high blood level of cephalothin (11.2-13.1 Mg/ml) persisted for about 3 weeks and the Coombs test remained positive. On September 21, 1970, the hematocrit had risen to 33.5%, the hemoglobin was 11.0 g/100 ml and the reticulocyte count was 2.2%. At that time, the cephalothin blood level was 0.04 /
Cephalothin-Induced Immune Hemolytic Anemia M. J eannet, A. B loch, J. M. D ayer, J. J. F arquet, J. P. G irard and A. C ruchaud Department of Medicine, Hôpital cantonal, Geneva
Key words. Cephalothin Immune reactions
Drug-induced hemolytic anemia • Hemolytic anemia •
Abstract. A patient with renal disease developed Coombs-positive hemolytic ane mia while receiving cephalothin therapy. An anti-cephalothin IgG antibody was de tected in the patient’s serum and in the eluates from her erythrocytes. In addition, nonimmunologic binding of normal and patient’s serum proteins to her own and cephalothin-coated normal red cells was demonstrated. Skin tests and in vitro lym phocyte stimulation revealed that the patient was sensitized to cephalothin and also to ampicillin. Careful investigation of drug-induced hemolytic anemias reveals the complexity of the immune mechanisms involved.
Downloaded by: UCL 144.82.238.225 - 5/7/2018 7:03:47 PM
Drug-induced immune hemolytic anemias are uncommun despite the fact that many drugs lead to the development of antibodies. However, some of these drugs, such as penicillin, bind firmly to red cells in vitro and more than 20 cases of penicillin-induced hemolytic anemia have been re ported [11]. Cephalothin and other cephalosporins which are chemically related to penicillin, also bind to red cells in vitro. Cephalothin sodium (Keflin) has been associated with a positive direct Coombs test in many patients receiving this antibiotic [4, 7] but only 2 cases of cephalothin and 1 case of cephalexin-induced immune hemolytic anemia have been re ported as yet [2, 5]. The purpose of this paper is to report an additional case of Coombs-positive hemolytic anemia related to cephalothin therapy and to define the characteristics of immunohematologic reactions to this drug.
110
J eannet/B loch/D ayer/F arquet/G irard/C ruchaud
Case Report A 61-year-old woman was admitted to the Hopital cantonal, Geneva, on June 3, 1970, because of weakness, nausea, vomiting and weight loss. Bilateral renal stones with chronic pyelonephritis and progressive renal failure had been diagnosed several years earlier. Physical examination was unremarkable, but laboratory investigations revealed an urinary infection and a severe renal failure with a blood urea nitrogen level of 77 mg/100 ml, a creatinine value of 6.2 mg/100 ml and a creatinine clear ance of 4 ml/min. Hyperparathyroidism was diagnosed and on July 3, 1970, parathyroidectomy was performed. The postoperative course was stormy with several episodes of re spiratory arrest requiring intubation and artificial ventilation, bronchopneumonia, cardiac arythmia, and acute pulmonary edema. From June 13 to July 12, 1970, the patient was treated with 500 mg ampicillin every 6 h; then from July 13 to July 28, 1970, 200 mg gentamycin were administered in 5 doses. From July 15, 1970 the pa tient was treated with cephalothin sodium, 4 g/day for 23 days. Before receiving cephalothin, the patient’s hematocrit level was 30%, the reticulocyte count was 1.3% and the Coombs test was negative. On August 4, 1970 after 21 days of cephalothin therapy, the hematocrit was 18.5% and hemoblogin 5.5 g/100 ml. Ten days later, the reticulocyte count was 16%. A direct Coombs test was positive using a standard an ti-whole serum and a specific anti-IgG reagent (table I). The serum complement was normal. Cephalothin therapy was discontinued on August 6, 1970, but a high blood level of cephalothin (11.2-13.1 Mg/ml) persisted for about 3 weeks and the Coombs test remained positive. On September 21, 1970, the hematocrit had risen to 33.5%, the hemoglobin was 11.0 g/100 ml and the reticulocyte count was 2.2%. At that time, the cephalothin blood level was 0.04 /
