Journal article
Dimeric FcγR ectodomains detect pathogenic anti-platelet factor 4-heparin antibodies in heparin-induced thromobocytopenia
Journal of Thrombosis and Haemostasis, Vol.16(12), pp.2520-2525
2018
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, so overdiagnosis can occur, with resulting inappropriate use of alternative anticoagulation 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 FcγRIIa (rsFcγRIIa) ectodomains for detecting HIT antibodies.
Patients/Methods
Plasma from 27 suspected HIT patients were tested for pathogenic anti‐PF4–heparin antibodies by binding of a novel dimeric FcγRIIa ectodomain probe. Plasmas were also tested by the use of PF4–heparin IgG ELISA, the HemosIL AcuStar HIT IgG‐specific assay, and a serotonin release assay (SRA).
Results
The dimeric rsFcγRIIa test produced no false positives and excluded four 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 being scored as false negatives. The improved discrimination of the novel assay over the IgG ELISA, which scored four false positives, supports the mechanistic interpretation that binding of dimeric rsFcγRIIa detects pairs of closely spaced IgG antibodies in PF4–heparin immune complexes.
Conclusions
This study found the cell‐free, function‐based dimeric rsFcγRIIa 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‐specific assay, warranting further evaluation of its potential to identify HIT in larger patient cohorts.
Details
- Title
- Dimeric FcγR ectodomains detect pathogenic anti-platelet factor 4-heparin antibodies in heparin-induced thromobocytopenia
- Authors/Creators
- B.D. Wines (Author/Creator) - Monash UniversityC.W. Tan (Author/Creator) - Royal Adelaide HospitalE. Duncan (Author/Creator) - Royal Adelaide HospitalS. McRae (Author/Creator) - Royal Adelaide HospitalR.I. Baker (Author/Creator) - Murdoch UniversityR.K. Andrews (Author/Creator) - Monash UniversityS. Esparon (Author/Creator) - Monash UniversityE.E. Gardiner (Author/Creator) - Australian National UniversityP.M. Hogarth (Author/Creator) - Monash University
- Publication Details
- Journal of Thrombosis and Haemostasis, Vol.16(12), pp.2520-2525
- Publisher
- Wiley-Blackwell
- Identifiers
- 991005541909407891
- Copyright
- © 2018 The Authors.
- Murdoch Affiliation
- School of Engineering and Information Technology
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.75 Blood Clotting
- 1.75.2119 Heparin-Induced Thrombocytopenia
- Web Of Science research areas
- Hematology
- Peripheral Vascular Disease
- ESI research areas
- Clinical Medicine