Publications & Reports

Dimeric FcgammaR ectodomains detect pathogenic platelet factor 4-heparin antibodies in heparin induced thromobocytopenia.

Wines BD, Tan CW, Duncan E, McRae S, Baker RI, Andrews RK, Esparon S, Gardiner EE, Hogarth PM
Immune Therapies Group, Burnet Institute, Melbourne, Vic, 3004, Australia.


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.

Link to publisher’s web site

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


  • Journal: Journal of Thrombosis and Haemostasis
  • Published: 30/09/2018
  • Volume: 16
  • Issue: 12
  • Pagination: 2520–2525