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Meta-Analysis
. 2022 Oct 26:379:e071594.
doi: 10.1136/bmj-2022-071594.

Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different covid-19 vaccines: international network cohort study from five European countries and the US

Xintong Li  1 , Edward Burn  2   3 , Talita Duarte-Salles  3 , Can Yin  4 , Christian Reich  4 , Antonella Delmestri  1 , Katia Verhamme  5 , Peter Rijnbeek  5 , Marc A Suchard  6   7 , Kelly Li  6 , Mees Mosseveld  5 , Luis H John  5 , Miguel-Angel Mayer  8 , Juan-Manuel Ramirez-Anguita  8 , Catherine Cohet  9 , Victoria Strauss  1 , Daniel Prieto-Alhambra  1   5
Affiliations
Meta-Analysis

Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different covid-19 vaccines: international network cohort study from five European countries and the US

Xintong Li et al. BMJ. .

Abstract

Objective: To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines.

Design: International network cohort study.

Setting: Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US.

Participants: Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021.

Main outcome measures: Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses.

Results: Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2.

Conclusions: In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the EMA for the submitted work; DP-A receives funding from the UK National Institute for Health Research (NIHR) in the form of a senior research fellowship and from the Oxford NIHR Biomedical Research Centre. XL receives the Clarendon Fund and Brasenose College scholarship (University of Oxford) to support her DPhil study. DP-A’s research group has received research grants from the EMA; Innovative Medicines Initiative; and Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, AstraZeneca, and UCB Biopharma. LHJ works for a research group who receives unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, Novartis, GSK, Chiesi, Astra-Zeneca, Amgen, Janssen Research and Development. PR works for a research group who receives unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, Novartis, GSK, Chiesi, Astra-Zeneca, Amgen, Janssen Research and Development. CC has no conflicts of interest. None of these declarations relate to the content of this paper.

Figures

Fig 1
Fig 1
Study cohort selection. Example shows data from the UK database Clinical Practice Research Datalink Aurum used to compare the risk of thrombocytopenia after a first dose of ChAdOx1-S vaccine (target) compared with a first dose of BNT162b2 vaccine (comparator)
Fig 2
Fig 2
Meta-analytical estimates of incidence rate ratios of developing thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events in the 28 days after covid-19 vaccination, according to information from routinely collected health databases. Lines with solid diamonds=calibrated estimates; lines with clear diamonds=uncalibrated estimates; TTS=thrombosis with thrombocytopenia syndrome; UK CPRD=Clinical Practice Research Datalink Aurum; Germany DA=IQVIA Disease Analyser Germany; Netherlands IPCI=Integrated Primary Care Information; France LPD=IQVIA Longitudinal Patient Data
See this image and copyright information in PMC

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