Abstract

BACKGROUND: Heparin induced thrombocytopenia (HIT) is a major and potentially fatal consequence of antibodies produced against platelet factor 4 (PF4)-heparin complexes following heparin exposure. Not all anti-PF4-heparin antibodies are pathogenic, hence over-diagnosis can occur with resulting inappropriate use of alternative anti-coagulation therapies that have associated risks of bleeding. However, definitive platelet functional assays are not widely available for routine analysis. OBJECTIVES: To assess the utility of dimeric recombinant soluble FcgammaRIIa ectodomains to detect HIT antibodies. PATIENTS/METHODS: Plasma from 27 suspected HIT patients were tested for pathogenic PF4-heparin antibodies by binding of a novel dimeric FcgammaRIIa ectodomain probe. Plasma were also tested by PF4-heparin IgG ELISA, HemosIL(®) AcuStar HIT-IgG assay and serotonin release assay (SRA). RESULTS: The dimeric rsFcgammaRIIa test produced no false positives and excluded 4 samples that were positive by IgG ELISA. In this small patient cohort the novel assay correctly assigned 93% of the suspected HIT patients with two of the HIT patients scored as false negatives. The improved discrimination of the novel assay over the IgG ELISA, which scored 4 false positives, supports the mechanistic interpretation that binding of dimeric rsFcgammaRIIa detects pairs of closely spaced IgG in PF4-heparin immune complexes. CONCLUSIONS: This study found the function-based dimeric rsFcgammaRIIa assay to be convenient, simple and potentially predictive of HIT. The assay had improved specificity over the IgG ELISA and correlated strongly with the Acustar HIT-IgG assay, so warranting further evaluation of its potential to identify HIT in larger patient cohorts. This article is protected by copyright. All rights reserved.

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This work was funded by the National Health and Medi-cal Research Council of Australia and the VictorianOperational Infrastructure Scheme