ORCID

Abstract

Background and Objective: Thrombotic thrombocytopenia syndrome (TTS) is a rare condition following vaccination with adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccines. This retrospective analysis of England primary care data aimed to estimate TTS event rates before, during, and after the COVID-19 pandemic, and following AZD1222 (ChAdOx1-nCoV-19) vaccination. Methods: Primary care data on TTS events were collected using the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network. TTS events were defined as thromboembolism with coincident (± 7 days) thrombocytopenia events using Systematized Nomenclature of Medicine clinical terms (the current Brighton Collaboration definition could not be used in the study as data related to specific parameters [e.g., D-dimer or PF4 antibodies] were not available in the primary care database). Multivariable logistic regression analyses were performed to assess the association between covariates and TTS. Results: Incident TTS rates per 100,000 person-years were: 0.42 in a pre-COVID-19 cohort (1 January, 2011–31 December, 2019; 9,062,313 individuals); 0 in 39,448 individuals with confirmed COVID-19 (1 July–31 December, 2020); 0.48 and 0.47 during the pre-vaccination pandemic period spanning 1 January–14 August, 2020 (13,245,710 individuals) and 15 August–31 December, 2020 (13,347,462 individuals); 2.41 in an AZD1222-vaccinated cohort (5,544,761 individuals; 1 January, 2021–4 July, 2022). Multivariable logistic regression analysis of TTS events (− 7/+ 42 days event-window; pre-COVID-19 cohort) showed greater odds in older individuals and high-risk groups as defined by the Joint Committee on Vaccination and Immunization. Thrombotic thrombocytopenia syndrome was rare in all cohorts. Differential covariate distributions precluded comparisons of TTS rates across cohorts. Covariate distributions within thromboembolism and thrombocytopenia cases were comparable to those of TTS cases. Conclusions: Our study, using a previous definition of TTS, reinforces the very rare nature of TTS before and during the pandemic, and before and after the introduction of the AZD1222 vaccine; it also confirms the established very low incident event rate in individuals vaccinated with AZD1222.

Publication Date

2025-01-01

Publication Title

Drug Safety

Volume

48

Issue

10

ISSN

0114-5916

Acceptance Date

2025-05-18

Deposit Date

2025-08-07

Funding

DL: during the conduct of this study, DL was an employee of and received a salary from PEPI Consultancy Ltd and funded by AstraZeneca Ltd, Ariello SRO, and Annexon Biosciences Inc. DL is now employed as the Drug Safety Lead at Lane Clark and Peacock (LCP) LLP, UK. DL is an Editorial Board member of Drug Safety. DL was not involved in the selection of peer reviewers for the manuscript nor in any of the subsequent editorial decisions. DC reports consulting fees from Oxford University Consulting and Bristol Myers Squibb, and grants from UK Research and Innovation, Wellcome Trust, NIHR, Hong Kong ITC, AstraZeneca, and Glaxo Smith Kline (GSK) and patents held by Oxford University Innovation. DC acknowledges funding from the NIHR Oxford Biomedical Research Centre. JMOM, DK, XF, FF, SNA, MJ, and AT have no conflicts of interest that are directly relevant to the content of this article. AA, AL, and LM are employees of AstraZeneca and may own stock/shares. SdL has received funding from AstraZeneca, Eli Lilly, GSK, Moderna, MSD, Novo Nordisk, Pfizer, Sanofi, Seqirus, and Takeda and been a member of advisory boards for GSK, Moderna, Sanofi, and Seqirus. He has had meeting expenses funded by AstraZeneca. This study was funded by AstraZeneca.

Keywords

ChAdOx1 nCoV-19/adverse effects, Humans, Middle Aged, Child, Preschool, England/epidemiology, Male, Incidence, Thrombocytopenia/epidemiology, Young Adult, Adolescent, Aged, 80 and over, Adult, COVID-19/prevention & control, Female, Aged, COVID-19 Vaccines/adverse effects, Retrospective Studies, Child, Purpura, Thrombotic Thrombocytopenic/epidemiology, Sentinel Surveillance, Cohort Studies

First Page

1161

Last Page

1175

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