title: Whole blood impedance aggregometry detects heparin-induced thrombocytopenia antibodies.
abstract: Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin use. IgG antibodies to complexes of platelet factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. Only a subset of these antibodies will activate platelets and these can only be identified with platelet aggregation (functional) assays. Heparin-induced platelet aggregation (HIPA) and (14)C-serotonin release (SRA) assays for HIT are time-consuming and complex to perform. We have developed a whole blood impedance (WBI) test using the new Multiplate analyser. All samples referred to our laboratory over a 10 month period were screened for heparin-PF4 antibodies by an ELISA method (Zymutest HIA IgG). The 4T's score was used to assess HIT pretest probability. Twenty antibody positive samples were further tested by all three functional assays: light transmission aggregometry (LTA), SRA and WBI. Thirteen out of twenty samples were positive by LTA (10 patients) and 15 by WBI (11 patients). SRA, considered to be the gold standard, was used as a confirmatory test and 11 were found to be positive (10 patients); four discrepant samples were weakly positive by WBI. The prevalence of a positive functional test was strongly correlated with the 4T's clinical risk score, but a small number of low-risk patients had positive functional assays. In this study, the WBI assay detected all SRA positive patients and was positive for two others suggesting greater sensitivity. The rapid and easy to perform assay may be a useful tool for haematology laboratories to detect platelet-activating HIT antibodies.
authors.affiliation: Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Northern Blood Research Centre, University of Sydney, St Leonards, NSW, Australia.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Morel-Kopp
authors.forename: Margaret
authors.initials: M
authors.lastname: Aboud
authors.forename: Chee Wee
authors.initials: CW
authors.lastname: Tan
authors.forename: Chandima
authors.initials: C
authors.lastname: Kulathilake
authors.forename: Christopher
authors.initials: C
authors.lastname: Ward
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000276:immunology*; D010979:Platelet Function Tests / Q000379:methods*; D010992:Plethysmography, Impedance / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D010978:Platelet Factor 4; D006493:Heparin