title: Performance characteristics of two commercially available IgG-specific immunoassays in the assessment of heparin-induced thrombocytopenia (HIT).
abstract: BACKGROUND
  The in vitro demonstration of antibodies against platelet factor-4/heparin (PF4/hep) complexes is an important contribution to the diagnosis of heparin-induced thrombocytopenia (HIT). The use of PF4/hep IgG-specific immunoassays enhances the specificity of HIT-investigations without any impairment of the sensitivity. Several IgG-specific immunoassays with different origin and structure of the target antigen-complex are commercially available.
  
  
  METHODS
  Using a retrospective cohort consisting of 459 patients suspected to have HIT, we compared the performance characteristics of two commercially available IgG-specific immunoassays, GTI- (Genetic Testing Institute) and HIA-IgG-ELISA (Hyphen Biomed Research).
  
  
  RESULTS
  PF4/hep antibodies were detected in 85 and 81 sera using GTI- and HIA-IgG-ELISA, respectively. OD values and clinical likelihood of patients who tested positive in one assay only were significantly lower than in those who tested positive in both immunoassays. Both IgG-specific assays showed high negative predictive values (100%) and similar but unsatisfactory positive predictive values, determined by a minimum clinical score of 5 and a positive HIPA result (41% and 43%, respectively). The implementation of a confirmatory step using excessive heparin increased the PPV of both assays, but results in a reduction of NPV in HIA-IgG-ELISA.
  
  
  CONCLUSIONS
  The detection of IgG antibodies alone improves the clinical usefulness of immunoassays. However, functional assays remain indispensable to avoid the overdiagnosis of HIT caused by the detection of IgG non-platelet activating antibodies. The OD value in IgG immunoassays appears to correlate with the clinical relevance of the antibodies and might be used as a predictive parameter in the assessment of HIT.
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University Giessen, Germany.
authors.forename: Tamam
authors.initials: T
authors.lastname: Bakchoul
authors.forename: Astrid
authors.initials: A
authors.lastname: Giptner
authors.forename: Gregor
authors.initials: G
authors.lastname: Bein
authors.forename: Sentot
authors.initials: S
authors.lastname: Santoso
authors.forename: Ulrich J H
authors.initials: UJ
authors.lastname: Sachs
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007074:Immunoglobulin G; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis*
chemical_list: D000925:Anticoagulants; D007074:Immunoglobulin G; D006493:Heparin