Publication date: Jul 31, 2025

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. 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. 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. 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.

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