title: The Role for Optical Density in Heparin-Induced Thrombocytopenia: A Cohort Study.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin utilization. An enzyme-linked immunosorbent assay (ELISA) is usually performed to assist in the diagnosis of HIT. ELISAs tend to be sensitive but lack specificity. We sought to use a new cutoff to define a positive HIT ELISA.
  
  
  METHODS
  We conducted a prospective observational study of hospitalized patients undergoing ELISA testing. All patients who underwent ELISA testing were eligible for inclusion (n = 496). Irrespective of the results, all subjects had confirmatory testing with a serotonin release assay (SRA). We compared a threshold optical density (OD) > 1.00 to the current definition of a positive ELISA (OD > 0.40) as a screening test for a positive SRA. We used sensitivity, specificity, and area under the receiver operating curve to determine whether an OD > 1.00 would improve diagnostic accuracy for HIT.
  
  
  RESULTS
  The SRA was positive in 10 patients (prevalence, 2.0%). Adjusting the definition of a positive HIT ELISA to > 1.00 maintained the sensitivity and negative predictive value at 100% in the cohort. The positive predictive value of the higher cutoff OD was more than triple the positive predictive value of an OD > 0.40 (41.7% vs 13.3%). No patient with a positive SRA had an OD measurement ≤ 1.00.
  
  
  CONCLUSIONS
  Increasing the OD threshold enhances specificity without noticeably compromising sensitivity. Altering the definition of the HIT ELISA could prevent unnecessary testing and/or treatment with non-heparin-based anticoagulants in patients with possible HIT.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT00946400; URL: www.clinicaltrials.gov.
authors.affiliation: Pulmonary and Critical Care Section, MedStar Washington Hospital Center, and Georgetown University Medical Center, Washington, DC. Electronic address: chee.m.chan@medstar.net.
authors.forename: Chee M
authors.initials: CM
authors.lastname: Chan
authors.affiliation: Pulmonary and Critical Care Section, MedStar Washington Hospital Center, and Georgetown University Medical Center, Washington, DC.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Woods
authors.affiliation: Department of Pathology and Molecular Medicine, Hamilton Regional Laboratory Program and McMaster University, Hamilton, ON, Canada.
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.affiliation: Department of Pathology and Molecular Medicine, Hamilton Regional Laboratory Program and McMaster University, Hamilton, ON, Canada.
authors.forename: Jo-Ann I
authors.initials: JI
authors.lastname: Sheppard
authors.affiliation: Pulmonary and Critical Care Section, MedStar Washington Hospital Center, and Georgetown University Medical Center, Washington, DC.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Shorr
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications / Q000175:diagnosis*
chemical_list: D000925:Anticoagulants; D006493:Heparin