title: Hemolytic events associated with intravenous immune globulin therapy: a qualitative analysis of 263 cases reported to four manufacturers between 2003 and 2012.
abstract: BACKGROUND
  Objectives of this study were to identify possible patient and product risk factors for intravenous immune globulin (IVIG)-associated hemolysis, a recognized side effect of IG therapy; analyze IVIG indications; and examine dose levels (g/kg body weight) and total IVIG dose administered.
  
  
  METHODS
  Reports of IVIG-associated hemolysis for 10 years (2003-2012) for four participating IG manufacturers were identified using a uniform case definition (Standardized MedDRA Query "Hemolytic disorders," Broad Scope, Version 16.0) and analyzed.
  
  
  RESULTS
  IVIG-associated hemolysis appears to occur predominantly at dose levels exceeding 0.5 g/kg, with 72% of cases with known dose information having dose levels between 1 and 2.5, and can affect patients at any age, without a clear gender preference. No association was found between hemagglutinin exposure and development of hemolysis, nor between dose levels and odds of receiving a transfusion to treat hemolysis. Patients with blood group AB may be at higher risk of hemolysis than those with group A or B.
  
  
  CONCLUSIONS
  Data examined confirm that IVIG-associated hemolysis predominantly occurs following infusion of high IVIG doses, and can affect patients at every age of both genders. While presence of hemagglutinins appears to play a major role in pathogenesis of hemolytic disorders, high hemagglutinin titers of IVIG products themselves seem to be of less relevance, indicating that the pathomechanism of IVIG-associated hemolysis may be related to the presence, but not the absolute amount, of hemagglutinins. Patients with hemolysis had additional hemolytic risks such as multiple comorbidities and medication use. IG-treated patients with multiple risks should be closely monitored for hemolysis.
authors.affiliation: Baxter Innovations GmbH, Vienna, Austria.
authors.forename: Roger
authors.initials: R
authors.lastname: Berg
authors.affiliation: CSL Behring, Marburg, Germany.
authors.forename: Amgad
authors.initials: A
authors.lastname: Shebl
authors.affiliation: Plasma Protein Therapeutics Association, Annapolis, Maryland.
authors.forename: Mary Clare
authors.initials: MC
authors.lastname: Kimber
authors.affiliation: Statistics Collaborative, Inc., Washington, DC.
authors.forename: Maria
authors.initials: M
authors.lastname: Abraham
authors.affiliation: Plasma Protein Therapeutics Association, Annapolis, Maryland.
authors.forename: George B
authors.initials: GB
authors.lastname: Schreiber
mesh_terms: D000017:ABO Blood-Group System / Q000097:blood; D005260:Female; D006388:Hemagglutinins / Q000008:administration & dosage / Q000009:adverse effects*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000017:ABO Blood-Group System; D006388:Hemagglutinins; D016756:Immunoglobulins, Intravenous