title: Comparison of an IgG-Specific Enzyme-Linked Immunosorbent Assay Cutoff of 0.4 Versus 0.8 and 1.0 Optical Density Units for Heparin-Induced Thrombocytopenia.
abstract: BACKGROUND
  Previous studies have demonstrated optimized diagnostic accuracy in utilizing higher antiheparin-platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) optical density (OD) thresholds for diagnosing heparin-induced thrombocytopenia (HIT). We describe the incidence of positive serotonin release assay (SRA) results, as well as performance characteristics, for antiheparin-PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units in the diagnosis of HIT at our institution.
  
  
  METHODS
  Following institutional review board approval, we conducted a single-center retrospective chart review on adult inpatients with a differential diagnosis of HIT evaluated by both antiheparin-PF4 ELISA and SRA from 2012 to 2014. The major endpoints were to assess incidence of positive SRA results, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy at antiheparin-PF4 ELISA values ≥0.4 OD units when compared to values ≥0.8 and ≥1.0 OD units. Clinical characteristics, including demographics, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected.
  
  
  RESULTS
  A total of 140 patients with 140 antiheparin-PF4 ELISA and SRA values were evaluated, of which 23 patients were SRA positive (16.4%) and 117 patients were SRA negative (83.6%). We identified a sensitivity of 91.3% versus 82.6% and 73.9%, specificity of 61.5% versus 87.2% and 91.5%, PPV of 31.8% versus 55.9% and 63.0%, NPV of 97.3% versus 96.2% and 94.7%, and accuracy of 66.4% versus 86.4% and 88.6% at antiheparin-PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units, respectively.
  
  
  CONCLUSIONS
  Our study suggests an increased antiheparin-PF4 ELISA threshold of 0.8 or 1.0 OD units enhances specificity, PPV, and accuracy while maintaining NPV with decreased sensitivity.
authors.affiliation: 1 Department of Pharmacy, Mayo Clinic, St Mary's Campus, Rochester, MN, USA.
authors.forename: Brianne M
authors.initials: BM
authors.lastname: Ritchie
authors.affiliation: 2 Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Connors
authors.affiliation: 3 Department of Pharmacy Services, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Katelyn W
authors.initials: KW
authors.lastname: Sylvester
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards*; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D057230:Limit of Detection; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced / Q000175:diagnosis*
chemical_list: D007074:Immunoglobulin G; D012701:Serotonin; D006493:Heparin
keywords: heparins; low-molecular-weight heparins; thrombocytopenia