title: What is the potential for overdiagnosis of heparin-induced thrombocytopenia?
abstract: Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4//heparin (PF4/H) complexes. According to the "iceberg model," only a subset of anti-PF4/heparin antibodies of IgG class evincing strong platelet-activating properties cause clinical HIT. Since many centers rely predominantly on an anti-PF4/polyanion enzyme-immunoassay (EIA) to diagnose HIT, we estimated the potential for overdiagnosis when only this single test is available. We examined a database of 100 patients in whom the probability of HIT had been estimated using a clinical scoring system (4Ts), and where patients underwent systematic testing for HIT antibodies using three assays: the platelet serotonin release assay (SRA), an "in-house" EIA that detects IgG anti-PF4/heparin antibodies (EIA-IgG), and a commercial EIA that detects anti-PF4/polyanion antibodies of all three immunoglobulin classes (EIA-GTI). Whereas 16 of 100 patients fulfilled a "classic" definition of HIT (intermediate/high probability plus strong platelet-activating anti-PF4/heparin IgG antibodies), an additional 16 patients fulfilled a "liberal" definition in which any investigated patient (irrespective of the pretest probability) who had a positive EIA-GTI was considered to have HIT. The clinical features of these 16 additional patients--including generally weak antibodies and low risk for thrombosis--suggest underlying non-HIT explanations for thrombocytopenia. Patients with a positive SRA generally corresponded to those with intermediate or high pretest probability of HIT who also had strong EIA-GTI reactivity (>1.20 OD units). We conclude there is the potential to overdiagnose HIT by approximately 100% if any positive EIA is considered to "confirm" the diagnosis of HIT irrespective of the clinical scenario.
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Lo
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Sigouin
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000276:immunology*; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D013927:Thrombosis / Q000453:epidemiology / Q000401:mortality
chemical_list: D001323:Autoantibodies; D010972:Platelet Activating Factor; D006493:Heparin