First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland

C R Simpson, T Shi, E Vasileiou, S V Katikireddi, S Kerr, E Moore, C McCowan, U Agrawal, S A Shah, L D Ritchie, J Murray, J Pan, D T Bradley, S J Stock, R Wood, A Chuter, J Beggs, H R Stagg, M Joy, R S M TsangS de Lusignan, R Hobbs, R A Lyons, F Torabi, S Bedston, M O'Leary, A Akbari, J McMenamin, C Robertson, A Sheikh

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Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.

Original languageEnglish
Pages (from-to)1290-1297
Number of pages8
JournalNature Medicine
Early online date9 Jun 2021
Publication statusPublished - Jul 2021

Bibliographical note

EAVE II is funded by the Medical Research Council (MC_PC_19075) with the support of BREATHE: the Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and the Community Health and Social Care Directorate of the Scottish Government. R.H. acknowledges support from the National Institute for Health Research (NIHR) School for Primary Care Research, the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford and the NIHR Oxford BREATHE Centre. We thank D. Kelly from Albasoft Limited for support with making primary care data available and J. Pickett, W. Inglis-Humphrey, V. Hammersley, M. Georgiou, L. Brook and L. Gonzalez Rienda for support with project management and administration. We thank the EAVE II Public Advisory Group. Our thanks to J. Quint, R. Al-Shahi Salman and Q. Hill for their help with reviewing code lists. Our thanks also to G. Schiff and L. Smeeth for reviewing this work before submission to the UK’s Medicines & Healthcare products Regulatory Agency.

Data availability
A data dictionary covering the datasets used in this study can be found at EAVE-II/EAVE-II- data-dictionary. The data that support the findings of this study are not publicly available because they are based on de-identified national clinical records. These are, however, available by application via Scotland’s National Safe Haven from Public Health Scotland. The data used in this study can be accessed by researchers through NHS Scotland’s Public Benefit and Privacy Panel via its Electronic Data Research and Innovation Service49.

Code availability
All code used in this study is publicly available at EAVE-II/Covid- vaccine-safety-haemo.


  • Adolescent
  • Adult
  • Aged
  • COVID-19/prevention & control
  • COVID-19 Vaccines/therapeutic use
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Hemorrhage/epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • Purpura, Thrombocytopenic, Idiopathic/epidemiology
  • SARS-CoV-2
  • Scotland/epidemiology
  • Sinus Thrombosis, Intracranial/epidemiology
  • Thrombocytopenia/epidemiology
  • Thromboembolism/epidemiology
  • Venous Thromboembolism/epidemiology
  • Young Adult


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