title: Using direct antiglobulin test results to reduce unnecessary cold agglutinin testing.
abstract: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by autoantibodies that preferentially react at 4°C. Laboratory testing for cold-reactive autoantibodies is laborious and may not be ordered judiciously, particularly in patients with a negative direct antiglobulin test (DAT). We sought to determine whether a negative DAT using anti-human complement (anti-C3) rules out elevated cold agglutinin (CA) titers and the diagnosis of CAD.
  
  
  
  We performed a retrospective study of patients with a CA test performed at three major academic medical centers: Barnes-Jewish Hospital (2003-2014), Vanderbilt University Medical Center (2007-2009), and Massachusetts General Hospital (2009-2014).
  
  
  
  This study included 801 patients, of whom 51% (n = 410) had a DAT within the 7 days before CA testing. A total of 98% of patients with a negative DAT using anti-C3 had a negative CA titer (<64). Only five subjects had a negative DAT using anti-C3 and an elevated CA titer.
  
  
  
  Overutilization of CA testing could be reduced by establishing laboratory acceptance criteria based on a positive DAT using anti-C3. Such acceptance criteria would have reduced CA testing by 68% for those with an available DAT result.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Wilen
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Garrett S
authors.initials: GS
authors.lastname: Booth
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Grossman
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: William J
authors.initials: WJ
authors.lastname: Lane
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Penny C
authors.initials: PC
authors.lastname: Szklarski
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Ronald
authors.initials: R
authors.lastname: Jackups
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000175:diagnosis / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D003298:Coombs Test; D003450:Cryoglobulins / Q000032:analysis / Q000276:immunology; D006801:Humans; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D003450:Cryoglobulins; C029443:cold agglutinins