Drug-induced haemolytic anemia.
Drug administration causes 16 to 18 per cent of cases of acquired immune haemolytic anaemia. The pathogenesis of erythrocyte sensitisation by drug-related antibody with or without fixation of complement is variable and there is a relationship between the responsible drug, the mechanism of red cell sensitisation, clinical manifestations, and laboratory methods of diagnosis. Drugs such as phenacetin and quinidine form a complex with the antidrug antibody, and the immune complex attaches to red cells usually fixing complement and causing acute intravascular haemolysis. Other drugs (e.g. penicillins) when given in high doses coat normal red cells in vivo and some patients develop a high titre IgG antidrug antibody which reacts with the coated cells. Haemolytic anaemia may develop, with red cell destruction being primarily extravascular. Cephalosporins cause positive direct antiglobulin tests in a small percentage of patients either by the same mechanism as penicillins or by modification of the red cell membrane leading to non-immunological absorption of serum proteins. Haemolytic anaemia has been reported only rarely. A few drugs (notably alpha-methyldopa) cause the development of autoimmune haemolytic anaemia. A knowledge of clinical manifestations and laboratory aids to diagnosis are necessary to distinguish immunohaematological abnormalities caused by drugs fron other causes. Drugs may also cause haemolytic anaemia by nonimmunologic mechanisms as a result of oxidative denaturation of haemoglobin. Factors which make red cells particularly susceptible to the effects of oxidant drugs are intraerythrocytic metabolic abnormalities or the presence of unstable haemoglobins.
D000743:Anemia, Hemolytic / Q000139:chemically induced* / Q000175:diagnosis; D001323:Autoantibodies / Q000032:analysis; D002512:Cephalothin / Q000009:adverse effects; D003298:Coombs Test; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004912:Erythrocytes / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications; D005978:Glutathione / Q000172:deficiency; D005980:Glutathione Reductase / Q000172:deficiency; D006386:Hemagglutination Tests; D006455:Hemoglobins, Abnormal / Q000378:metabolism; D006801:Humans; D007105:Immune Complex Diseases; D008750:Methyldopa / Q000009:adverse effects; D010406:Penicillins / Q000009:adverse effects; D010734:Phosphogluconate Dehydrogenase / Q000172:deficiency
D001323:Autoantibodies; D006455:Hemoglobins, Abnormal; D010406:Penicillins; D008750:Methyldopa; D010734:Phosphogluconate Dehydrogenase; D005980:Glutathione Reductase; D005978:Glutathione; D002512:Cephalothin