A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic Anemia in the FDA Adverse Event Reporting System

Abstract

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. Objective: This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term “anaemias haemolytic immune” according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). Results: There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. Conclusions: Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.

Consumo de Antibióticos y su Relación con el Desarrollo de Anemia Hemolítica Autoinmune

“…La anemia hemolítica autoinmune asociada a fármacos es extremadamente rara. Sin embargo, la administración inadecuada de tratamientos antibióticos prolongados generan resistencia antimicrobiana, en el consumo de recursos sanitarios y efectos adversos graves incluyendo condiciones autoinmunes como la anemia hemolítica autoinmunitaria, la cual un efecto adverso hematológico farmacogenético poco común pero potencialmente mortal (13) (14). Los antibióticos asociados más frecuentemente a la anemia hemolítica inmunitaria son cefotetan, ceftriaxona y piperacilina (15).…”

Ceftriaxone-induced severe hemolytic anemia, renal calculi, and cholecystolithiasis in a 3-year-old child: a case report and literature review

“…In studies involving patients with autoimmune hemolytic anemia (AIHA), drug-induced immune hemolytic anemia (DIIHA) constitutes approximately 10% of the total cases (Hill et al, 2017). More than 130 drugs are suspected to trigger immune hemolytic anemia (IHA) (Maquet et al, 2024), with ceftriaxone being the 11th most common cause in children, occurring at a rate of approximately 1.5 cases per million in population (Tang et al, 2023). Compared to the rare incidence of ceftriaxone-induced IHA, ceftriaxone-induced renal calculi and cholecystolithiasis are relatively more common.…”