Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ ETIOLOGY AND PATHOGENESIS ++ 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 24–1 lists the drugs implicated in the production of a positive direct antiglobulin test and accelerated red cell destruction. Table 24–2 summarizes the four mechanisms of drug-induced immune interaction with the red cell surface. ++Table Graphic Jump LocationTABLE 24–1ASSOCIATION BETWEEN DRUGS AND POSITIVE DIRECT ANTIGLOBULIN TESTS*View Table||Download (.pdf) TABLE 24–1 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 Omeprazole 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, 9th ed, Chap. 54, Table 54–2. ++Table Graphic Jump LocationTABLE 24–2MAJOR MECHANISMS OF DRUG-RELATED HEMOLYTIC ANEMIA AND POSITIVE DIRECT ANTIGLOBULIN TESTSView Table||Download (.pdf) TABLE 24–2 MAJOR MECHANISMS OF DRUG-RELATED HEMOLYTIC ANEMIA AND POSITIVE DIRECT ANTIGLOBULIN TESTS Hapten/Drug Adsorption Ternary Complex Formation Autoantibody Binding Nonimmunologic Protein Adsorption Prototype drug Penicillin Quinidine α-Methyldopa Cephalothin Role of drug Binds to red cell membrane Forms ternary complex with antibody and red cell membrane component Induces formation of antibody to native red cell antigen Possibly alters red cell membrane Drug affinity to cell Strong Weak None demonstrated to intact red cell but binding to membranes reported Strong Antibody to drug Present Present Absent Absent Antibody class predominating IgG IgM or IgG IgG None Proteins detected by direct antiglobulin test IgG, rarely complement Complement IgG, rarely complement Multiple plasma proteins Dose of drug associated with positive antiglobulin test High Low High High Presence of drug required for indirect antiglobulin test Yes (coating test red cells) Yes (added to test medium) No Yes (added to test medium) Mechanism of red cell destruction Splenic sequestration of IgG-coated red cells Direct lysis by complement plus splenic–hepatic clearance of C3b-coated ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Download the Access App: iOS | Android Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.