Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content ++ ETIOLOGY AND PATHOGENESIS ++ Table 26–1 lists the drugs implicated in the production of a positive direct antiglobulin test and accelerated red cell destruction. Three mechanisms of drug-related immunologic injury to red cells are defined: — Hapten/drug adsorption involving drug-dependent antibodies. — Ternary complex formation involving drug-dependent antibodies. — Induction of autoantibodies that react with red cells in the absence of the inciting drug. Drug-related nonimmunologic protein adsorption may also result in a positive direct antiglobulin test without red cell injury. ++Table Graphic Jump LocationTABLE 26–1ASSOCIATION BETWEEN DRUGS AND POSITIVE DIRECT ANTIGLOBULIN TESTS*View Table|Favorite Table|Download (.pdf) TABLE 26–1 ASSOCIATION BETWEEN DRUGS AND POSITIVE DIRECT ANTIGLOBULIN TESTS* Drugs Hapten or Drug Adsorption Mechanism Penicillins Carbromal Cephalosporins Tolbutamide Tetracycline Cianidanol 6-Mercaptopurine Hydrocortisone Oxaliplatin Ternary Complex Mechanism Stibophen Probenecid Quinine Nomifensine Quinidine Cephalosporins Chlorpropamide Diethylstilbestrol Rifampicin Amphotericin B Antazoline Doxepin Thiopental Diclofenac Tolmetin Etodolac Metformin Hydrocortisone Oxaliplatin Pemetrexed Autoantibody Mechanism Cephalosporins Cianidanol Tolmetin Latamoxef Nomifensine Glafenine α-Methyldopa Procainamide l-Dopa Diclofenac Mefenamic acid Pentostatin Teniposide Fludarabine Oxaliplatin Cladribine Efalizumab Lenalidomide Nonimmunologic Protein Adsorption Cephalosporins Cisplatin Oxaliplatin Carboplatin Uncertain Mechanism of Immune Injury Mesantoin Streptomycin Phenacetin Ibuprofen Insecticides Triamterene Chlorpromazine Erythromycin Melphalan 5-Fluorouracil Isoniazid Nalidixic acid p-Aminosalicylic acid Sulindac Acetaminophen Omeprazol Thiazides Temafloxacin Efavirenz Carboplatin *It is not always possible to infer the mechanism of immune injury induced by a drug. Moreover, some drugs can act by more than one mechanism. In cases of uncertain mechanism, the cited drug use is coincident with the hemolytic anemia, and causality is inferred, not established experimentally. These cases are included so that the reader may be aware of these potential associations.Source: Williams Hematology, 8th ed, Chap. 53, Table 53–2, p. 780. ++ HAPTEN OR DRUG ADSORPTION MECHANISM ++ Occurs with drugs that bind firmly to red cell membrane proteins. Penicillin is the classic example. In patients receiving high-dose penicillin, red cells have a substantial coating of the drug. In a small proportion of patients, an antipenicillin antibody (usually IgG) develops and binds to the penicillin on the red cell. The direct antiglobulin test then becomes positive and hemolytic anemia may ensue. Hemolytic anemia caused by penicillin typically occurs after 7 to 10 days of treatment and ceases a few days to 2 weeks once the drug is stopped. Other manifestations of penicillin allergy are usually not present. Antibody-coated ("opsonized") red cells are destroyed mainly in the spleen. Antibodies eluted from red cells, or present in sera, react only against penicillin-coated red cells. This specificity distinguishes drug-dependent antibodies from true autoantibodies. Hemolytic anemia similar to that seen with penicillin has also been ascribed to other drugs (see Table 26–1). ++ TERNARY COMPLEX MECHANISM: DRUG-ANTIBODY TARGET-CELL COMPLEX ++ The mechanism of red cell injury is not clearly defined, but it appears to be mediated by a cooperative interaction to generate a ternary complex involving the drug or drug-metabolite, a drug-binding ... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. What is MyAccess? Create a FREE MyAccess profile to: Use this site remotely Bookmark your favorite content Track your self-assessment progress and more!