title: Pitfalls in the diagnosis of heparin-Induced thrombocytopenia: A 6-year experience from a reference laboratory.
abstract: Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies against complexes of platelet factor 4 (PF4) and heparin. The diagnosis of HIT is contingent on accurate and timely laboratory testing. Recently, alternative anticoagulants for the treatment of HIT have been introduced along with algorithms for better HIT diagnosis. However, the increased reliance on immunoassays for the diagnosis of HIT may have harmful consequences due to the high rate of false positive results. To compare trends and implications of current HIT testing approaches, we analyzed results over a six-year period from the McMaster University Platelet Immunology Reference Laboratory. From 2008 to 2013, 8,546 samples were investigated for HIT using both an in-house IgG-specific anti-PF4/heparin enzyme immunoassay (EIA) and the serotonin-release assay (SRA). Of 8,546 samples tested, 13.4% were true-positives (positive in both assays); 65.6% were true-negatives (negative in both assays); 20.9% were presumed false positive for HIT (EIA-positive/SRA-negative); and 0.2% were EIA-negative/SRA-positive. The frequency of EIA-positive/SRA-negative results increased over time (from 12.9% in 2008 to 22.9% in 2013). We found that the number of SRA-negative samples was reduced from referring centers that used an immunoassay as an initial screen; however, 41% of those samples tested negative in the immunoassay and in the SRA at the reference laboratory. The suspicion of HIT continues at a high rate and the agreement between the EIA and SRA test results remains problematic.
authors: Department of Medicine. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Ishac
authors: I
authors: Nazi
authors: Department of Medicine. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.|Canadian Blood Services, Hamilton, Ontario, Canada.
authors: Donald M
authors: DM
authors: Arnold
authors: Department of Medicine. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Jane C
authors: JC
authors: Moore
authors: Department of Medicine. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: James W
authors: JW
authors: Smith
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Nikola
authors: N
authors: Ivetic
authors: Department of Medicine. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Peter
authors: P
authors: Horsewood
authors: Department of Medicine. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Theodore E
authors: TE
authors: Warkentin
authors: Department of Medicine. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: John G
authors: JG
authors: Kelton
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects; D001681:Biological Assay / Q000706:statistics & numerical data; D001792:Blood Platelets / Q000276:immunology / Q000473:pathology; D003951:Diagnostic Errors; D005189:False Positive Reactions; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D007118:Immunoassay / Q000706:statistics & numerical data; D007074:Immunoglobulin G / Q000032:analysis* / Q000096:biosynthesis; D012189:Retrospective Studies; D012701:Serotonin / Q000032:analysis* / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D007074:Immunoglobulin G; D012701:Serotonin; D006493:Heparin