Drug-induced hemolytic anemia due to ceftriaxone in a patient with recently identified alloantibodies: A diagnostic challenge

Transfusion. 2026 Jul;66(7):1444-1448. doi: 10.1111/trf.70222. Epub 2026 Apr 10.

Abstract

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening condition resulting from destruction of red blood cells (RBCs) following drug exposure. Although the precise incidence is difficult to ascertain because of under-diagnosis and under-reporting, estimates suggest an annual incidence of 1 in 1 million. This may be because often only patients with dramatic or severe hemolysis typically undergo comprehensive immunohematologic evaluation, including diagnostic drug testing. In patients receiving blood transfusions, making a diagnosis can be even more challenging as hemolysis may be complicated by concurrent alloimmunization.

Case report: We present the case of a 51-year-old female with recently identified anti-E and anti-M alloantibodies who developed severe hemolytic anemia 3 days after blood transfusion, ultimately leading to multi-organ failure and death. Although initially suspected to be due to a delayed hemolytic transfusion reaction, further immunohematology testing confirmed ceftriaxone-induced immune hemolytic anemia.

Conclusion: This case highlights how DIIHA can be masquerading as a delayed hemolytic transfusion reaction, underscoring the importance of considering DIIHA as a differential diagnosis, especially in patients receiving commonly implicated drugs, so that they can be promptly discontinued to avoid adverse outcomes. Confirmatory testing can be done and is usually available at an immunohematology reference laboratory.

Keywords: ceftriaxone; drug induced immune hemolytic anemia; immunohematology.

Publication types

  • Case Reports

MeSH terms

  • Anemia, Hemolytic* / chemically induced
  • Anemia, Hemolytic* / diagnosis
  • Anemia, Hemolytic* / immunology
  • Anemia, Hemolytic, Autoimmune* / chemically induced
  • Anemia, Hemolytic, Autoimmune* / diagnosis
  • Anti-Bacterial Agents* / adverse effects
  • Ceftriaxone* / adverse effects
  • Fatal Outcome
  • Female
  • Humans
  • Isoantibodies* / blood
  • Isoantibodies* / immunology
  • Middle Aged

Substances

  • Isoantibodies
  • Ceftriaxone
  • Anti-Bacterial Agents