Problems in pre-transfusion tests related to drugs and chemicals

Ingestion of drugs can cause patients or blood donors to have a positive direct and sometimes indirect antiglobulin test. The most common cause of these positive reactions and immune hemolytic anemia due to drugs is the formation of red cell autoantibodies. These autoantibodies will react with the patient's own red cells and usually most other normal red cells in vitro without the drug being present. The prototype drug causing this type of reaction is alpha methyldopa (Aldomet). Other drugs cause positive antiglobulin tests by three different mechanisms, the drug antibodies reacting with red cells in vitro only in the presence of the drug. The first of these mechanisms causes positive reactions because the drug binds firmly to the red cell membrane, and antibody against the drug will combine with the drug on the membrane leading to IgG-sensitized red cells. The prototype drug for this mechanism is penicillin. The second mechanism involves chemical modification of the red cell membrane by the drug so that it takes up many proteins nonspecifically; the cephalosporins are the only group of drugs known to react in this fashion. The final mechanism involves the formation of an immune complex by the drug and its specific antibody. This immune complex will attach to cell membranes, usually activating complement in the process. Examples of drugs thought to operate by this mechanism are phenacetin, quinine, and quinidine. Some individuals have antibodies present in their serum that will react with chemical added to commercial blood bank reagents. Examples of these are antibodies to dyes added to ABO typing sera, antibodies to sodium caprylate in bovine albumin, and antibodies to chemicals added to red cell diluents, e.g., chloramphenicol, neomycin, and hydrocortisone. If these antibodies are present they can create problems in pretransfusion testing; in particular, they can present anomalies in ABO, Rh grouping, and antibody detection.