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


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.


International network cohort study.


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


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.


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.


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.

Author list



  1. Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
  2. Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
  3. Real World Solutions, IQVIA, Durham, NC, USA
  4. Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
  5. Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA
  6. Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, USA
  7. Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute, Faculty of Health and Life Sciences, University of Pompeu Fabra, Barcelona, Spain
  8. Data Analytics and Methods Task Force, European Medicines Agency, Amsterdam, Netherlands


Xintong Li, doctoral student1, Edward Burn, senior researcher1 2, Talita Duarte-Salles, senior epidemiologist2, Can Yin, data scientist3, Christian Reich, principal investigator3, Antonella Delmestri, lead health data scientist1, Katia Verhamme, associate professor4, Peter Rijnbeek, professor4, Marc A Suchard, professor5 6, Kelly Li, doctoral student5, Mees Mosseveld, software engineer4, Luis H John, doctoral student4, Miguel-Angel Mayer, associate professor7, Juan-Manuel Ramirez-Anguita, senior data scientist7, Catherine Cohet, pharmacoepidemiologist8, Victoria Strauss, lead statistician1, Daniel Prieto-Alhambra, professor1 4

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