Ordóñez-Mena José M, Kar Debasish, Fan Xuejuan, Ferreira Filipa, Anand Sneha N, Layton Deborah, Clifton David, Joy Mark, Thakur Anshul, Alessi Anu, Lee Andrew, Mather Lisa, de Lusignan Simon
Clinical Informatics and Health Outcomes Research Group, Nuffield Department of Primary Care Health Sciences, University of Oxford, Eagle House, Walton Well Road, Oxford, OX2 6ED, UK.
Community and Primary Care Research Group, University of Plymouth, Plymouth, UK.
Drug Saf. 2025 Oct;48(10):1161-1175. doi: 10.1007/s40264-025-01566-1. Epub 2025 Jul 31.
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.
血栓性血小板减少综合征(TTS)是接种腺病毒载体2019冠状病毒病(COVID-19)疫苗后出现的一种罕见病症。这项对英格兰初级医疗数据的回顾性分析旨在估计COVID-19大流行之前、期间和之后以及接种AZD1222(ChAdOx1-nCoV-19)疫苗后的TTS事件发生率。
使用牛津皇家全科医师学院研究与监测中心哨点网络收集有关TTS事件的初级医疗数据。TTS事件被定义为使用医学系统命名法临床术语的血栓栓塞合并(±7天)血小板减少事件(由于初级医疗数据库中没有与特定参数[如D-二聚体或PF4抗体]相关的数据,本研究无法使用当前布莱顿协作组的定义)。进行多变量逻辑回归分析以评估协变量与TTS之间的关联。
每10万人年的TTS发病率分别为:COVID-19大流行前队列(2011年1月1日至2019年12月31日;9,062,313人)中为0.42;39,448例确诊COVID-19患者(2020年7月1日至12月31日)中为0;在2020年1月1日至8月14日(13,245,710人)和2020年8月15日至12月31日(13,347,462人)的疫苗接种前大流行期间分别为0.48和0.47;在接种AZD1222的队列(5,544,761人;2021年1月1日至2022年7月4日)中为2.41。对TTS事件(-7/+42天事件窗口;COVID-19大流行前队列)的多变量逻辑回归分析显示,老年人和疫苗接种与免疫联合委员会定义的高危人群中发生TTS的几率更高。血栓性血小板减少综合征在所有队列中均很罕见。不同的协变量分布妨碍了各队列之间TTS发生率的比较。血栓栓塞和血小板减少病例中的协变量分布与TTS病例的协变量分布相当。
我们的研究使用TTS的先前定义,强化了大流行之前和期间以及AZD1222疫苗引入之前和之后TTS非常罕见的性质;它还证实了接种AZD1222的个体中既定的极低发病率。