Drug-induced immune neutropenia/agranulocytosis

Immunohematology. 2014;30(2):95-101.


Neutrophils are the most abundant white blood cell in blood and play a critical role in preventing infections as part of the innate immune system. Reduction in neutrophils below an absolute count of 500 cells/pL is termed severe neutropenia or agranulocytosis. Drug-induced immune neutropenia (DIIN) occurs when drug-dependent antibodies form against neutrophil membrane glycoproteins and cause neutrophil destruction. Affected patients have fever, chills, and infections; severe infections left untreated can result in death. Treatment with granulocyte colony-stimulating factor can hasten neutrophil recovery. Cumulative data show that severe neutropenia or agranulocytosis associated with exposure to nonchemotherapy drugs ranges from approximately 1.6 to 15.4 cases per million population per year. Drugs most often associated with neutropenia or agranulocytosis include dipyrone, diclofenac, ticlopidine, calcium dobesilate, spironolactone, antithyroid drugs (e.g., propylthiouracil), carbamazepine, sulfamethoxazole- trimethoprim, [3-lactam antibiotics, clozapine, levamisole, and vancomycin. Assays used for detection of neutrophil drug-dependent antibodies (DDAbs) include flow cytometry, monoclonal antibody immobilization of granulocyte antigens, enzyme-linked immunosorbent assay, immunoblotting, granulocyte agglutination, and granulocytotoxicity. However, testing for neutrophil DDAbs is rarely performed owing to its complexity and lack of availability. Mechanisms proposed for DIIN have not been rigorously studied, but those that have been studied include drug- or hapten-induced antibody formation and autoantibody production against drug metabolite or protein adducts covalently attached to neutrophil membrane proteins. This review will address acute, severe neutropenia caused by neutrophil-reactive antibodies induced by nonchemotherapy drugs-DIIN

Publication types

  • Review

MeSH terms

  • Autoantibodies / blood*
  • Cell Membrane / drug effects
  • Cell Membrane / immunology
  • Drug-Related Side Effects and Adverse Reactions*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Leukocyte Count
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology
  • Neutropenia / chemically induced*
  • Neutropenia / diagnosis
  • Neutropenia / drug therapy
  • Neutropenia / immunology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Protein Binding


  • Autoantibodies
  • Membrane Glycoproteins
  • Granulocyte Colony-Stimulating Factor