Case Report: Diagnosis and detection of amoxicillin-induced immune hemolytic anemia

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially severe adverse reaction, with antibiotics being common culprits. Amoxicillin, a widely used β-lactam antibiotic, has been infrequently reported to cause DIIHA, posing diagnostic challenges due to its nonspecific presentation. Objective: This study aimed to report a case of amoxicillin-induced DIIHA, detailing the diagnostic approach and laboratory methods for detecting drug-dependent antibodies. Methods: A 60-year-old female presented with jaundice, dark urine, and severe anemia following amoxicillin administration. Laboratory investigations included direct and indirect antiglobulin tests, antibody screening and identification, and drug-specific antibody detection using amoxicillin-sensitized red blood cells and drug-added assays. Clinical causality was assessed using the Naranjo Adverse Drug Reaction Probability Scale. Results: The patient's direct antiglobulin test was weakly positive for IgG without C3d activation. Serum showed pan-reactivity in saline, which resolved after dithiothreitol treatment, suggesting the presence of IgM cold antibodies. Serum reacted positively with amoxicillin-coated red cells in the indirect antiglobulin test but not with untreated cells, confirming the presence of amoxicillin-dependent antibodies. Hemoglobin and bilirubin levels improved after amoxicillin discontinuation. The Naranjo score was 7, indicating a "probable" association between amoxicillin and hemolysis. Conclusion: Amoxicillin can induce immune hemolytic anemia through a drug-dependent antibody mechanism. A combination of detailed drug history, serological testing, and drug-specific assays is essential for accurate diagnosis. Immediate withdrawal of the implicated drug remains critical for clinical recovery.