Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study

Abstract

Objective: To assess rates of cardiovascular and haemostatic events in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S in Denmark and Norway and to compare them with rates observed in the general populations.

Design: Population based cohort study.

Setting: Nationwide healthcare registers in Denmark and Norway.

Participants: All people aged 18-65 years who received a first vaccination with ChAdOx1-S from 9 February 2021 to 11 March 2021. The general populations of Denmark (2016-18) and Norway (2018-19) served as comparator cohorts.

Main outcome measures: Observed 28 day rates of hospital contacts for incident arterial events, venous thromboembolism, thrombocytopenia/coagulation disorders, and bleeding among vaccinated people compared with expected rates, based on national age and sex specific background rates from the general populations of the two countries.

Results: The vaccinated cohorts comprised 148 792 people in Denmark (median age 45 years, 80% women) and 132 472 in Norway (median age 44 years, 78% women), who received their first dose of ChAdOx1-S. Among 281 264 people who received ChAdOx1-S, the standardised morbidity ratio for arterial events was 0.97 (95% confidence interval 0.77 to 1.20). 59 venous thromboembolic events were observed in the vaccinated cohort compared with 30 expected based on the incidence rates in the general population, corresponding to a standardised morbidity ratio of 1.97 (1.50 to 2.54) and 11 (5.6 to 17.0) excess events per 100 000 vaccinations. A higher than expected rate of cerebral venous thrombosis was observed: standardised morbidity ratio 20.25 (8.14 to 41.73); an excess of 2.5 (0.9 to 5.2) events per 100 000 vaccinations. The standardised morbidity ratio for any thrombocytopenia/coagulation disorders was 1.52 (0.97 to 2.25) and for any bleeding was 1.23 (0.97 to 1.55). 15 deaths were observed in the vaccine cohort compared with 44 expected.

Conclusions: Among recipients of ChAdOx1-S, increased rates of venous thromboembolic events, including cerebral venous thrombosis, were observed. For the remaining safety outcomes, results were largely reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding, which could be influenced by increased surveillance of vaccine recipients. The absolute risks of venous thromboembolic events were, however, small, and the findings should be interpreted in the light of the proven beneficial effects of the vaccine, the context of the given country, and the limitations to the generalisability of the study findings.

Fig 1

General population incidence rates, observed and expected counts of events, excess events per 100 000 vaccinations, and standardised morbidity ratios of arterial events, venous thromboembolism, and all cause mortality within 28 days of vaccination in a cohort of 18-65 year old Danish and Norwegian people (n=281 264) receiving their first dose of the Oxford-AstraZeneca vaccine (ChAdOx1-S). NR=not reported owing to privacy regulations. *Per 1000 person years in the general population. †Observed events are not mutually exclusive (ie, one patient can contribute to two different third level outcomes. However, two different third level outcomes would only count once towards a common second level outcome, and similarly only once in a first level outcome). ‡Expected events based on incidence rates in the general population. §Full name: Occlusion and stenosis of precerebral or cerebral arteries, not resulting in cerebral infarction. ¶Including angiitis hypersensitiva, angiitis hypersensitiva with Schönlein-Henochs purpura, Buerger’s syndrome, Goodpasture syndrome, microangiopathia thrombotica, other necrotising vasculitis, and thrombotic thrombocytopenic purpura. **Including embolism and thrombosis in non-specified veins, embolism and thrombosis in other specified veins, and embolism and thrombosis of caval vein

Fig 2

General population incidence rates, observed and expected counts of events, excess events per 100 000 vaccinations, and standardised morbidity ratios of thrombocytopenia/coagulation disorders and bleeding events within 28 days of vaccination in a cohort of 18-65 year old Danish and Norwegian people (n=281 264) receiving their first dose of the Oxford-AstraZeneca covid-19 vaccine (ChAdOx1-S). NR=not reported owing to privacy regulations. *Per 1000 person years in the general population. †Observed events are not mutually exclusive (ie, one patient can contribute to two different third level outcomes. However, two different third level outcomes would only count once towards a common second level outcome, and similarly only once in a first level outcome). ‡Expected events based on incidence rates in the general population. §Not available in the Norwegian data source. ^¶Including haemolytic anaemia, haemolytic uraemic syndrome, and paroxysmal nocturnal haemoglobinuria

Fig 3

Results from supplementary analyses restricted to subgroups of patients on sex, and age, shorter follow-up, and excluding brief hospital contacts. NR=not reported owing to privacy regulations. *Per 1000 person years in the general population. †Observed events are not mutually exclusive (ie, one patient can contribute to two different third level outcomes. However, two different third level outcomes would only count once towards a common second level outcome, and similarly only once in a first level outcome). ‡Expected events based on incidence rates in the general population. §The general population comparison cohort was followed from January 2020 through March 2021 in both countries