[Drug-induced immune hemolytic anemia: a retrospective study of 10 cases]

Rev Med Interne. 2014 Dec;35(12):779-89. doi: 10.1016/j.revmed.2014.05.009. Epub 2014 Jun 5.
[Article in French]


Purpose: Drug-induced immune haemolytic anemia occurs in one case per million and can be fatal. Our aim was to describe the main characteristics and the type of drug involved.

Methods: Cases were retrospectively identified using spontaneous notifications collected by our pharmacovigilance centre and the results of immuno-hematological investigations performed by the laboratory of French blood establishment of Lyon between 2000 and 2012. Inclusion criteria were: an immune (positive direct antiglobulin test), hemolytic, anemia (haemoglobin <100 g/L), with at least a plausible causal relationship with drug exposure according to the French method of imputability or the presence of drug-dependent antibodies, and exclusion of other causes of hemolysis.

Results: Ten cases (5 men and 5 women, median age 54.4 years) were identified. Causal drugs were ambroxol, beta-interferon, cefotetan, ceftriaxone, loratadine, oxacillin, oxaliplatine, piperacillin-tazobactam, pristinamycin, and quinine. The median time to onset of anemia after starting the culprit drug was 6 days (2 hours to 16 days). The median nadir of hemoglobin was 57.9 g/L (range: 34-78). The direct antiglobulin test was positive in 8 patients: IgG only (n=4), IgG and complement (n=3), and IgA (n=1). Drug-induced immune haemolytic anemia was considered as definite in 5 cases with positive drug-induced antibodies, probable in 4 cases negative for the detection of drug-induced antibodies but with plausible or likely causal relationship with drug exposure, and probable with an autoimmune mechanism in 1 case.

Conclusion: The diagnosis of DIIHA is often difficult because of the similarities with autoimmune haemolytic anemia and the inconstant sensitivity of immunologic tests that sometimes required repetitive assessment.

Keywords: Antibodies; Anticorps; Anémie hémolytique; Direct antiglobulin test; Drug; Haemolytic anemia; Médicament; Test de Coombs.

Publication types

  • English Abstract

MeSH terms

  • Anemia, Hemolytic / chemically induced*
  • Anemia, Hemolytic / immunology*
  • Antibodies / blood
  • Drug-Related Side Effects and Adverse Reactions*
  • Female
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Retrospective Studies


  • Antibodies
  • Immunoglobulin A
  • Immunoglobulin G