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

Abstract

ObjectiveTo 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.DesignPopulation based cohort study.SettingNationwide healthcare registers in Denmark and Norway.ParticipantsAll 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 measuresObserved 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.ResultsThe 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.ConclusionsAmong 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.

Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following Adenovirus Vector COVID-19 Vaccination: Interim Guidance for Healthcare Professionals in Emergency Department and Inpatient Settings

“…Published estimates of the incidence of VITT range from 1 case per 26,000 to 1 case per 127,000 doses of AstraZeneca/COVISHIELD administered. [3][4][5][6] There have been few reported cases of VITT with the Janssen/Johnson & Johnson vaccine thus far, so it is challenging to calculate a precise frequency, but the incidence of VITT appears to be approximately 1 case per 500,000 vaccine doses administered. 7 What symptoms should make you suspect VITT?…”

Arterial and Venous Thrombosis in COVID-19 Disease: From Molecular Pathway to Vaccine Administration

“…Pottegard and colleagues [131] assessed rates of hemostatic events in a cohort of 148792 vaccinated population from Denmark and compared them with general population cohorts from Denmark and Norway. Results showed 59 venous thromboembolic events in the vaccinated cohort compared with 30 expected based on general incidence rates.…”

“…In particular, higher rates of cerebral venous thrombosis were observed: the standardised morbidity ratio for it was demonstrated to be 20.25 (8.14 to 41.73). Interestingly, the rate of death was superior for the general population: 44 cases versus 15 for the vaccinated group [131] Increased surveillance of them could justify these numbers and prove the beneficial effects of ChadOx1 vaccine outweigh the risks.…”

AstraZeneca COVID-19 vaccine-related thromboembolism

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The Oxford-AstraZeneca COVID-19 vaccine [AZD-1222; ChAdOx1-S] is associated with a small risk of venous thromboembolism, say authors of a retrospective study published in the BMJ. 1 Data from nationwide healthcare registers in Denmark and Norway were used to assess rates of cardiovascular and haemostatic events reported within 28 days after vaccination with ChAdOx1-S between 9 February and 11 March 2021 in adults 18-65 years of age in Denmark (n=148 792) and Norway (132 472), compared with rates of these events in the general population in each country.Overall, 83 cases of arterial adverse events were observed after vaccination and 86 cases were expected (standardised morbidity ratio [SMR] 0.97; 95% CI 0.77, 1.20), and there was no significant increase in the rate of myocardial infarction or ischaemic heart disease. The rate of cerebral haemorrhage was increased (SMR 2.33; 95% CI 1.01, 4.59), resulting in 1.7 excess events per 100 000 vaccinations.Venous thromboembolism was reported in a significantly greater number of vaccinated adults than expected cases based on the incidence rate in the general population (n=59 vs 30; SMR 1.97; 95% CI 1.50, 2.54), resulting in 11 excess cases per 100 000 vaccinations.

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“…The Oxford-AstraZeneca COVID-19 vaccine [AZD-1222; ChAdOx1-S] is associated with a small risk of venous thromboembolism, say authors of a retrospective study published in the BMJ. 1 Data from nationwide healthcare registers in Denmark and Norway were used to assess rates of cardiovascular and haemostatic events reported within 28 days after vaccination with ChAdOx1-S between 9 February and 11 March 2021 in adults 18-65 years of age in Denmark (n=148 792) and Norway (132 472), compared with rates of these events in the general population in each country.…”