Thrombocytopenic, thromboembolic and haemorrhagic events following second dose with BNT162b2 and ChAdOx1: self-controlled case series analysis of the English national sentinel cohort

Mark Joy; Utkarsh Agrawal; Xuejuan Fan; Chris Robertson; Sneha N Anand; Jose Ordonez-Mena; Rachel Byford; Rosalind Goudie; Gavin Jamie; Debasish Kar; John Williams; Gemma L Marsden; Victoria Tzortziou-Brown; Sir Aziz Sheikh; F D Richard Hobbs; Simon de Lusignan

doi:10.1016/j.lanepe.2023.100681

Thrombocytopenic, thromboembolic and haemorrhagic events following second dose with BNT162b2 and ChAdOx1: self-controlled case series analysis of the English national sentinel cohort

Lancet Reg Health Eur. 2023 Jul 18:32:100681. doi: 10.1016/j.lanepe.2023.100681. eCollection 2023 Sep.

Authors

Mark Joy¹, Utkarsh Agrawal¹, Xuejuan Fan¹, Chris Robertson^{2

3}, Sneha N Anand¹, Jose Ordonez-Mena¹, Rachel Byford¹, Rosalind Goudie¹, Gavin Jamie¹, Debasish Kar¹, John Williams¹, Gemma L Marsden⁴, Victoria Tzortziou-Brown⁴, Sir Aziz Sheikh⁵, F D Richard Hobbs¹, Simon de Lusignan¹

Affiliations

¹ Nuffield Department of Primary Care Health Sciences, University of Oxford, UK.
² Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK.
³ Public Health Scotland, Glasgow, UK.
⁴ Royal College of General Practitioners, London, UK.
⁵ Usher Institute, The University of Edinburgh, Edinburgh, UK.

Abstract

Background: Thrombosis associated with thrombocytopenia was a matter of concern post first and second doses of BNT162b2 and ChAdOx1 COVID-19 vaccines. Therefore, it is important to investigate the risk of thrombocytopenic, thromboembolic and haemorrhagic events following a second dose of BNT162b2 and ChAdOx1 COVID-19 vaccines.

Methods: We conducted a large-scale self-controlled case series analysis, using routine primary care data linked to hospital data, among 12.3 million individuals (16 years old and above) in England. We used the nationally representative Oxford-Royal College of General Practitioners (RCGP) sentinel network database with baseline and risk periods between 8th December 2020 and 11th June 2022. We included individuals who received two vaccine (primary) doses of the BNT162b2 mRNA (Pfizer-BioNTech) and two vaccine doses of ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in our analyses. We carried out a self-controlled case series (SCCS) analysis for each outcome using a conditional Poisson regression model with an offset for the length of risk period. We reported the incidence rate ratios (IRRs) and 95% confidence intervals (CI) of thrombocytopenic, thromboembolic (including arterial and venous events) and haemorrhagic events, in the period of 0-27 days after receiving a second dose of BNT162b2 or ChAdOx1 vaccines compared to the baseline period (14 or more days prior to first dose, 28 or more days after the second dose and the time between 28 or more days after the first and 14 or more days prior to the second dose). We adjusted for a range of potential confounders, including age, sex, comorbidities and deprivation.

Findings: Between December 8, 2020 and February 11, 2022, 6,306,306 individuals were vaccinated with two doses of BNT162b2 and 6,046,785 individuals were vaccinated with two doses of ChAdOx1. Compared to the baseline, our analysis show no increased risk of venous thromboembolic events (VTE) for both BNT162b2 (IRR 0.71, 95% CI: 0.65-0.770) and ChAdOx1 (IRR 0.91, 95% CI: 0.84-0.98); and similarly there was no increased risk for cerebral venous sinus thrombosis (CVST) for both BNT162b2 (IRR 0.87, 95% CI: 0.41-1.85) and ChAdOx1 (IRR 1.73, 95% CI: 0.82-3.68). We additionally report no difference in IRR for pulmonary embolus, and deep vein thrombosis, thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), and haemorrhagic events post second dose for both BNT162b2.

Interpretation: Reassuringly, we found no associations between increased risk of thrombocytopenic, thromboembolic and haemorrhagic events post vaccination with second dose for either of these vaccines.

Funding: Data and Connectivity: COVID-19 Vaccines Pharmacovigilance study.

Keywords: COVID-19 vaccines; Epidemiology; Vaccine safety.