Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study

Hippisley-Cox, Julia; Patone, Martina; Mei, Xue W; Saatci, Defne; Dixon, Sharon; Khunti, Kamlesh; Zaccardi, Francesco; Watkinson, Peter; Shankar-Hari, Manu; Doidge, James; Harrison, David A; Griffin, Simon J; Sheikh, Aziz; Coupland, Carol A C

Abstract

Objective: To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults.

Design: Self-controlled case series study using national data on covid-19 vaccination and hospital admissions.

Setting: Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom’s health service (NHS).

Participants: 29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study.

Main outcome measures: The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events.

Results: The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test.

Conclusion: Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.

Citation

Hippisley-Cox, J., Patone, M., Mei, X. W., Saatci, D., Dixon, S., Khunti, K., …Coupland, C. A. C. (2021). Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. BMJ, 374, Article n1931. https://doi.org/10.1136/bmj.n1931

• Journal Article Type: Article
• Acceptance Date: Aug 2, 2021
• Online Publication Date: Aug 27, 2021
• Publication Date: 2021
• Deposit Date: Aug 31, 2021
• Publicly Available Date: Sep 6, 2021
• Journal: BMJ
• Print ISSN: 0959-8138
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 374
• Article Number: n1931
• DOI: https://doi.org/10.1136/bmj.n1931
• Keywords: thrombocytopenia, thromboembolism, covid-19 vaccination, SARS-CoV-2 positive testing
• Public URL: https://nottingham-repository.worktribe.com/output/6136970
• Publisher URL: https://www.bmj.com/content/374/bmj.n1931