title: Performance characteristics of an automated latex immunoturbidimetric assay [HemosIL®HIT-Ab(PF4-H)] for the diagnosis of immune heparin-induced thrombocytopenia.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating anti-PF4/heparin antibodies. Given time-sensitive treatment considerations, a rapid and accurate laboratory test for HIT antibodies is needed.
  
  
  OBJECTIVE
  To determine operating characteristics for the HemosIL®HIT-Ab(PF4/H), a rapid, on-demand, fully-automated, latex immunoturbidimetric assay (LIA), for diagnosis of HIT.
  
  
  METHODS
  We evaluated LIA sensitivity, specificity, negative (NPV) and positive predictive value (PPV), negative (LR-) and positive likelihood ratio (LR+), using citrated-plasma from 429 patients (prospective cohort study of 4Ts scoring; HIT, n=31), and from consecutive HIT patients (n=125), using reference standard serotonin-release assay (SRA). Comparators included two PF4-dependent enzyme-immunoassays (EIAs). We used stratum-specific likelihood ratios (SSLRs) to determine how differing magnitudes of LIA-positivity influenced post-test probability of HIT.
  
  
  RESULTS
  LIA operating characteristics were: sensitivity=97.4% (152/156); specificity=94.0% (374/398); PPV=55.6% (30/54); and NPV=99.7% (374/375). At manufacturers' cutoffs, LIA specificity and PPV were superior to the EIAs. Although a negative LIA pointed strongly against HIT (LR-, 0.034), the post-test probability was ~2% with high 4Ts score. The LIA's LR+ was high (16.0), with SSLRs rising substantially with greater LIA-positivity: 5.7 (1.0-4.9U/mL), 31 (5.0-15.9U/mL), and 128 (≥16U/mL). A LIA-positive result (at 1.0 cutoff) indicated at least 24% HIT probability (low 4Ts score), rising to 90% with high 4Ts score.
  
  
  CONCLUSIONS
  Although approximately 1 in 40 SRA-positive patients tested LIA-negative, the LIA's high NPV and PPV indicate that this rapid assay is useful for the diagnostic evaluation of HIT, including in low pre-test situations.
authors.affiliation: Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Centre for Transfusion Research, Hamilton, Ontario, Canada. Electronic address: twarken@mcmaster.ca.
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.affiliation: Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jo-Ann I
authors.initials: JI
authors.lastname: Sheppard
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; Thrombosis & Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
authors.forename: Lori-Ann
authors.initials: LA
authors.lastname: Linkins
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Centre for Transfusion Research, Hamilton, Ontario, Canada; Canadian Blood Services, Hamilton, Ontario, Canada.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Arnold
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Centre for Transfusion Research, Hamilton, Ontario, Canada.
authors.forename: Ishac
authors.initials: I
authors.lastname: Nazy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology; D000925:Anticoagulants / Q000009:adverse effects* / Q000276:immunology; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D000074024:Immunoturbidimetry / Q000191:economics / Q000379:methods*; D007840:Latex / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000276:immunology; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000139:chemically induced* / Q000175:diagnosis* / Q000276:immunology; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D007840:Latex; D010978:Platelet Factor 4; D006493:Heparin
keywords: Enzyme-immunoassay; Heparin-induced thrombocytopenia; Latex immunoturbidimetric assay; Rapid assay