ORCID Profile
0000-0002-3851-9364
Current Organisation
Australian National University
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Publisher: Wiley
Date: 06-2020
DOI: 10.1111/IJLH.13197
Publisher: Elsevier BV
Date: 03-2023
Publisher: American Society of Hematology
Date: 02-2018
DOI: 10.1182/BLOODADVANCES.2017011171
Abstract: Soluble GPVI is elevated in patients with thermal injury with sepsis, and sGPVI levels augment severity score prediction of mortality. The GPVI ligand, fibrin, induces GPVI shedding without requirement for platelet activation or signaling
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1111/JTH.15881
Abstract: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus-based vaccines aimed to prevent and minimize COVID-19 and related pathophysiology. To describe patterns of testing for anti-platelet factor 4 (PF4) antibodies using various ELISA assays in a large Australian cohort and comparative functional platelet activation assays in a subset. Asserachrom HPIA IgG ELISA was performed in 1284 patients over a period of 12 months, supplemented in select cohorts by comparative ELISA using three other methods (n = 78-179), three different functional assays (flow cytometry, serotonin release assay, and/or Multiplate n = 476), and rapid immunological chemiluminescence anti-PF4 assay (n = 460), in a multicenter study. For first episode presentations, 190/1284 (14.8%) ELISA tests were positive. Conversely, most (445/460 96.7%) chemiluminescence anti-PF4 test results were negative. All functional assays showed associations of higher median ELISA optical density with functional positivity and with high rates of ELISA positivity (64.0% to 85.2%). Data also identified functional positivity in 14.8%-36.0% of ELISA negative s les, suggesting false negative VITT by HPIA IgG ELISA in upward of one third of assessable cases. To our knowledge, this is the largest multicenter evaluation of anti-PF4 testing for investigation of VITT. Discrepancies in test results (ELISA vs. ELISA or ELISA vs. functional assay) in some patients highlighted limitations in relying on single methods (ELISA and functional) for PF4 antibody detection in VITT, and also highlights the variability in phenotypic test presentation and pathomechanism of VITT.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1111/JTH.15650
Publisher: Elsevier BV
Date: 06-2020
DOI: 10.1111/JTH.14797
Publisher: Springer US
Date: 2023
Publisher: Elsevier BV
Date: 05-2023
Publisher: Springer Science and Business Media LLC
Date: 27-05-2016
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1002/RTH2.12033
Publisher: American Society of Hematology
Date: 10-06-2022
DOI: 10.1182/BLOODADVANCES.2021006698
Abstract: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe prothrombotic complication of adenoviral vaccines, including the ChAdOx1 nCoV-19 (Vaxzevria) vaccine. The putative mechanism involves formation of pathological anti–platelet factor 4 (PF4) antibodies that activate platelets via the low-affinity immunoglobulin G receptor FcγRIIa to drive thrombosis and thrombocytopenia. Functional assays are important for VITT diagnosis, as not all detectable anti-PF4 antibodies are pathogenic, and immunoassays have varying sensitivity. Combination of ligand binding of G protein–coupled receptors (protease-activated receptor-1) and immunoreceptor tyrosine–based activation motif–linked receptors (FcγRIIa) synergistically induce procoagulant platelet formation, which supports thrombin generation. Here, we describe a flow cytometry–based procoagulant platelet assay using cell death marker GSAO and P-selectin to diagnose VITT by exposing donor whole blood to patient plasma in the presence of a protease-activated receptor-1 agonist. Consecutive patients triaged for confirmatory functional VITT testing after screening using PF4/heparin ELISA were evaluated. In a development cohort of 47 patients with suspected VITT, plasma from ELISA-positive patients (n = 23), but not healthy donors (n = 32) or in iduals exposed to the ChAdOx1 nCov-19 vaccine without VITT (n = 24), significantly increased the procoagulant platelet response. In a validation cohort of 99 VITT patients identified according to clinicopathologic adjudication, procoagulant flow cytometry identified 93% of VITT cases, including ELISA-negative and serotonin release assay–negative patients. The in vitro effect of intravenous immunoglobulin (IVIg) and fondaparinux trended with the clinical response seen in patients. Induction of FcγRIIa-dependent procoagulant response by patient plasma, suppressible by heparin and IVIg, is highly indicative of VITT, resulting in a sensitive and specific assay that has been adopted as part of a national diagnostic algorithm to identify vaccinated patients with platelet-activating antibodies.
No related grants have been discovered for Christine Lee.