Assessment of immunological anti-platelet factor 4 antibodies for vaccine-induced thrombotic thrombocytopenia (VITT) in a large Australian cohort: A multicenter study comprising 1284 patients.

Autor: Favaloro EJ; Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Sydney Centres for Thrombosis and Haemostasis, NSW Health Pathology, Westmead Hospital, Westmead, New South Wales, Australia.; School of Dentistry and Medical Sciences, Faculty of Science and Health, Charles Sturt University, Wagga, New South Wales, Australia.; School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia., Clifford J; Haematology, Monash Health, Melbourne, Victoria, Australia., Leitinger E; Haematology, Monash Health, Melbourne, Victoria, Australia., Parker M; Haematology, Monash Health, Melbourne, Victoria, Australia., Sung P; Haematology, Monash Health, Melbourne, Victoria, Australia., Chunilal S; Haematology, Monash Health, Melbourne, Victoria, Australia., Tran H; Clinical Haematology Department, The Alfred Hospital, Melbourne, Victoria, Australia., Kershaw G; Haematology, NSW Health Pathology, Prince Alfred Hospital, Camperdown, New South Wales, Australia., Fu S; Haematology, NSW Health Pathology, Prince Alfred Hospital, Camperdown, New South Wales, Australia., Passam F; Haematology, NSW Health Pathology, Prince Alfred Hospital, Camperdown, New South Wales, Australia., Ahuja M; Haematology, NSW Health Pathology, St George Hospital, Kogarah, New South Wales, Australia., Ho SJ; Haematology, NSW Health Pathology, St George Hospital, Kogarah, New South Wales, Australia., Duncan E; Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Yacoub O; Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Tan CW; Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.; University of Adelaide, Adelaide, South Australia, Australia., Kaminskis L; Haematology, PathWest, Fiona Stanley Hospital, Perth, Western Australia, Australia., Modica N; Haematology, PathWest, Fiona Stanley Hospital, Perth, Western Australia, Australia., Pepperell D; Haematology, PathWest, Fiona Stanley Hospital, Perth, Western Australia, Australia., Ballard L; Haematology, Qld Pathology, Royal Brisbane Hospital, Brisbane, Queensland, Australia., Clarke L; Haematology, NSW Health Pathology, Concord Hospital, Concord, New South Wales, Australia.; Australian Red Cross Lifeblood, Sydney, New South Wales, Australia., Lee CSM; ANZAC Research Institute, University of Sydney, Concord Hospital, Concord, New South Wales, Australia., Gardiner EE; John Curtin School of Medical Research, Division of Genome Sciences and Cancer, The Australian National University, Canberra, Australian Capital Territory, Australia., Young-Ill Choi P; John Curtin School of Medical Research, Division of Genome Sciences and Cancer, The Australian National University, Canberra, Australian Capital Territory, Australia.; Haematology, The Canberra Hospital, Canberra, Australian Capital Territory, Australia., Tohidi-Esfahani I; ANZAC Research Institute, University of Sydney, Concord Hospital, Concord, New South Wales, Australia., Bird R; Division of Cancer Services, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia., Brighton T; Haematology, NSW Health Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia., Chen VM; Haematology, NSW Health Pathology, Concord Hospital, Concord, New South Wales, Australia.; ANZAC Research Institute, University of Sydney, Concord Hospital, Concord, New South Wales, Australia.
Jazyk: angličtina
Zdroj: Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2022 Dec; Vol. 20 (12), pp. 2896-2908. Date of Electronic Publication: 2022 Sep 29.
DOI: 10.1111/jth.15881
Abstrakt: Background: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus-based vaccines aimed to prevent and minimize COVID-19 and related pathophysiology.
Objectives: 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.
Patients/methods: 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.
Results: 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 samples, suggesting false negative VITT by HPIA IgG ELISA in upward of one third of assessable cases.
Conclusion: 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.
(© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)
Databáze: MEDLINE
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