Ceftriaxone-induced immune hemolytic anemia

Ann Pharmacother. 2014 Dec;48(12):1594-604. doi: 10.1177/1060028014548310. Epub 2014 Aug 27.


Objectives: To describe a case of ceftriaxone-induced immune hemolytic anemia (CIIHA) in a 6 year-old boy with sickle cell disease (SCD) and perform a systematic literature review to delineate the clinical and laboratory features of this condition.

Data sources: EMBASE (1947-January 2014), MEDLINE (1946-January 2014), and databases from the US Food and Drug Administration and Health Canada were searched, using anemia, hemolytic anemia, hemolysis, and ceftriaxone as search terms. Additional references were identified from a review of literature citations.

Study selection and data extraction: All case reports and observational studies describing clinical and laboratory features of CIIHA were included.

Data synthesis: A total of 37 eligible reports of CIIHA were identified, including our index case, and 70% were children. Mortality was 30% in all age groups and 64% in children. The majority of patients had underlying conditions (70%), of which SCD was most commonly reported. Previous ceftriaxone exposure was reported in 65%. Common features included elevated lactate dehydrogenase (70%); early, new-onset hemoglobinuria (59%); acute renal failure (46%); positive direct antibody testing (70%); and anticeftriaxone antibodies (68%). Also, 32% had a preceding, unrecognized, hemolytic episode associated with ceftriaxone.

Summary: Given the common use of ceftriaxone worldwide, knowledge of CIIHA, which often goes undiagnosed until late in the course, is essential for clinicians. Based on the findings of this review, we suggest obtaining past history of ceftriaxone exposures and screening for new-onset hemoglobinuria during ceftriaxone therapy in selected patients as potential methods for early diagnosis of this rare but potentially fatal condition.

Keywords: adverse drug reactions; ceftriaxone; ceftriaxone-induced immune hemolytic anemia; cephalosporins; drug-induced immune hemolytic anemia; sickle cell disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Hemolytic, Autoimmune / chemically induced*
  • Anemia, Hemolytic, Autoimmune / immunology
  • Anemia, Sickle Cell / complications
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / immunology
  • Autoantibodies / blood*
  • Ceftriaxone / adverse effects*
  • Ceftriaxone / immunology
  • Child
  • Humans
  • Male
  • Respiratory Tract Infections / complications
  • Respiratory Tract Infections / drug therapy


  • Anti-Bacterial Agents
  • Autoantibodies
  • Ceftriaxone