Possible mechanisms for intravenous immunoglobulin-associated hemolysis: clues obtained from review of clinical case reports

Transfusion. 2015 Jul:55 Suppl 2:S59-64. doi: 10.1111/trf.13090.

Abstract

Background: Intravenous immunoglobulin (IVIG) is an efficacious treatment modality for a number of conditions and is usually well tolerated with few reports of serious adverse events; however, the administration of IVIG may occasionally result in clinically significant hemolysis.

Study design and methods: The literature was reviewed for case reports and case series of IVIG-associated hemolysis. The cases were scrutinized for clues as to the possible mechanism(s) of the hemolysis.

Results: Review of the 129 individual cases reported in the literature identifies clinical features shared by the majority of patients. These features included non-O blood group patients and treatment with high-dose IVIG as an immune-modulating agent for an underlying inflammatory or immune-mediated disorder. Other patient factors such as secretor phenotype, soluble ABH substance, and Fcgamma receptor polymorphisms may also play a role.

Conclusions: It is known that high-dose IVIG given to non-O blood group patients with underlying inflammatory and/or immune-mediated disorders is associated with increased risk of hemolysis. This review reveals additional patient characteristics in cases of IVIG-associated hemolysis, including underrepresentation of D- and group B cases, higher incidence in pediatric Kawasaki disease and unique at-risk patient groups including allogeneic stem cell transplant recipients with group A donor in a group O recipient, and patients in whom soluble AB substance is removed by plasma exchange at the same time as receiving IVIG.

Publication types

  • Review

MeSH terms

  • ABO Blood-Group System* / immunology
  • Adult
  • Allografts
  • Female
  • Hemolysis / drug effects
  • Hemolysis / genetics
  • Hemolysis / immunology
  • Humans
  • Immunoglobulins, Intravenous / adverse effects*
  • Immunoglobulins, Intravenous / immunology
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / adverse effects*
  • Immunologic Factors / immunology
  • Immunologic Factors / therapeutic use
  • Incidence
  • Male
  • Mucocutaneous Lymph Node Syndrome / drug therapy
  • Mucocutaneous Lymph Node Syndrome / genetics
  • Mucocutaneous Lymph Node Syndrome / immunology
  • Polymorphism, Genetic*
  • Receptors, IgG* / genetics
  • Receptors, IgG* / immunology
  • Stem Cell Transplantation

Substances

  • ABO Blood-Group System
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Receptors, IgG