Serologic characteristics of ceftriaxone antibodies in 25 patients with drug-induced immune hemolytic anemia

BACKGROUND: Ceftriaxone, a third‐generation cephalosporin, is commonly used to prevent and treat infections. Since 1987, it has been the second most common cause of drug‐induced immune hemolytic anemia (DIIHA) investigated in our laboratory. STUDY DESIGN AND METHODS: Samples from 79 patients (1987‐2010), suspected of having DIIHA caused by ceftriaxone, were studied for the presence of ceftriaxone antibodies. Direct antiglobulin tests (DATs) and tests with ceftriaxone‐treated red blood cells (RBCs) or untreated and enzyme‐treated RBCs in the presence of ceftriaxone were performed. RESULTS: Twenty‐five (32%) of the 79 patients had antibodies to ceftriaxone detected. Seventeen (68%) of the 25 patients were children; reactions in children were usually dramatic and severe. Nine (36%) of the 25 patients had fatal DIIHA. Nineteen of the 25 samples had DATs performed by our laboratory; 100% of samples were reactive with anti‐C3 and 47% were reactive with anti‐IgG. All 25 sera had ceftriaxone antibodies detected when testing untreated or ficin‐treated RBCs in the presence of ceftriaxone (resulting in agglutination, hemolysis or sensitization of test RBCs). These antibodies were primarily IgM and reactivity was enhanced by testing ficin‐treated RBCs. Sixteen (64%) of the 25 sera reacted with test RBCs when no ceftriaxone was added in vitro; this was most likely due to the transient presence of drug or drug‐immune complexes in the patient's circulation at the time that the blood samples were drawn. CONCLUSION: Ceftriaxone antibodies can cause severe intravascular hemolysis. Complement can usually be detected on the patient's RBCs and IgM antibodies are usually detected in the patient's serum.