PB0343 - Longitudinal study on the persistence of anti-platelet factor 4 antibodies in vaccine-induced immune thrombotic thrombocytopenia after 14 months

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Michael H. Hack

MSc candidate
Department of Biochemistry and Biomedical Sciences, McMaster University Hamilton, Ontario, Canada
Hamilton, Ontario, Canada

Co-Author(s)

Yi Zhang (she/her/hers)

MSc Candidate
Department of Biochemistry and Biomedical Sciences, McMaster University Hamilton, Ontario, Canada
Hamilton, Ontario, Canada
RC

Rumi Clare

Research Associate
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
Hamilton, Ontario, Canada
NI

Nikola Ivetic

Postdoctoral Fellow
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
Hamilton, Ontario, Canada
HB

Hina Bhakta

Research Technician
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
Hamilton, Ontario, Canada
KL

Kayla Lucier

Clinical Research Coordinator
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
Hamilton, Ontario, Canada
MC

Monique Chiam

Research Technician
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
Hamilton, Ontario, Canada
JK

John G. Kelton

Professor
Faculty of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
Hamilton, Ontario, Canada
Donald Arnold, MD MSc (he/him/his)

Professor
McMaster University, Department of Medicine
HAMILTON, Ontario, Canada
Ishac Nazy, PhD

Associate Professor
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada,
Hamilton, Ontario, Canada

Background: Adenoviral vector-based SARS-CoV-2 vaccines have been associated with a rare but severe adverse effect known as vaccine-induced immune thrombotic thrombocytopenia (VITT) and characterized by thrombocytopenia and thrombosis. VITT closely resembles another immunological disorder caused by exposure to the anticoagulant heparin, known as heparin-induced thrombocytopenia (HIT). Both disorders are caused by platelet-activating antibodies directed against a chemokine contained in platelets known as platelet factor 4 (PF4/CXCL4).

Aims: As HIT anti-PF4 antibodies last 50 - 80 days after heparin exposure, this study seeks to determine the durability of VITT anti-PF4 antibodies.

Methods: VITT patient blood samples from across Canada were collected longitudinally post-vaccination with an adenoviral vector-based SARS-CoV-2 vaccine. VITT patient samples were tested for anti-PF4 antibodies using the Immucor IgG/A/M enzyme immunoassay (EIA; positive OD ≥ 0.4) and the ability of patient serum to activate platelets was measured using the PF4-serotonin release assay (SRA; positive 14C-serotonin release ≥ 20%).

Results: Follow-up samples from 24 VITT patients were collected, 11 (45.8%) were female and 13 (54.2%) were male with a mean age of 50.9 years (range 37.7 – 72.3 years); twenty-three (95.8%) received at least one dose of AZD1222 ChAdOx1 nCoV-19 (AstraZeneca) and 1 (4.2%) received Ad26.COV2.S (Janssen/Johnson & Johnson). Of the VITT follow-up samples tested, 18/24 (75%) remained positive for anti-PF4 antibodies with a mean OD of 1.389 (range 0.471 - 2.724 OD) and of those 7/18 (38.9%) were found to also have platelet activating antibodies in the PF4-SRA, even after a mean of 434 days (range 34 - 611 days) post-vaccination with an adenoviral vector-based SARS-CoV-2 vaccine.

Conclusion(s): Unlike anti-PF4 antibodies seen in HIT, VITT anti-PF4 antibodies persist for much longer and elucidating the longevity of VITT antibodies will help predict the likelihood of relapse and significantly improve long-term outcomes for those living with this relatively new disorder.