AstraZeneca vaccine: EMA opinion

The EMA considers that the benefit-risk balance of AstraZeneca's COVID-19 vaccine remains positive, and that, overall, there is no association with thromboembolic disorders.

AstraZeneca COVID-19 vaccine: benefits still outweigh risks despite possible link to rare cases of thrombosis and thrombocytopenia

The EMA considers that the benefit-risk balance of AstraZeneca's COVID-19 vaccine remains positive, and that, overall, there is no association with thromboembolic disorders. However, the vaccine package insert will be updated with information on cases of DIC (disseminated intravascular coagulation) and CVST (cerebral venous sinus thrombosis) that have occurred.

Health care professionals should pay close attention to possible cases of thromboembolism, DIC or CVST occurring in vaccinated individuals. Vaccinated individuals should be warned of the possibility and should immediately contact their doctor if they show signs of thromboembolism, especially signs of thrombocytopenia and cerebral thrombosis, such as bruising, bleeding tendency and persistent or severe headache, particularly after 3 days of vaccination.

The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has concluded its preliminary investigation into reports of thrombus formation in people vaccinated with AstraZeneca's COVID-19 vaccine. The committee confirmed that:

On the last point, these cases are rare. As of 16 March, some 20 million people in the UK and Europe have been vaccinated with the AstraZeneca vaccine, but the EMA has investigated only seven cases of DIC and 18 cases of CVST. A causal link to the vaccine is not proven, but it is possible and merits further analysis.

The PRAC investigation involved haematology experts from other health authorities including the UK Medicines and Healthcare products Regulatory Agency (MHRA), which has overseen the administration of this vaccine to some 11 million people. Overall, the number of thrombotic events reported after vaccination, both in pre-authorisation studies and in reports following the launch of vaccination campaigns (469 reports, including 191 from the European Union), was lower than expected in the general population. This allows the PRAC to confirm that there is no increased overall risk of thrombus formation. However, some concerns remain in younger patients, particularly related to these rare cases.

The committee experts reviewed in great detail the DIC and CVST registrations reported by the member states, 9 of which resulted in death. Most of these events occurred in people under 55 years of age, the majority being women. Since these events are rare, and COVID-19 itself often causes blood clotting disorders, it is difficult to estimate a background rate for these events in people who did not take the vaccine. However, based on pre-COVID data, it was calculated that by 16 March one could expect less than 1 case of DIC among people under 50 years of age within 14 days of vaccine administration, instead 5 cases were reported. Similarly, an average of 1.35 CVST cases could have been expected among this age group, whereas by the same cut-off date there had been 12. A similar imbalance was not seen in the older vaccinated population.

The committee considered that the vaccine's proven efficacy in preventing hospitalisation and death due to COVID-19 outweighed the extremely low probability of developing DIC or CVST. However, in light of its findings, patients should be aware of the remote possibility of such syndromes, and if symptoms suggestive of clotting problems occur, patients should seek immediate medical attention and inform health care providers of their recent vaccination. Steps are already being taken to update the vaccine information to include these risks.

The PRAC will undertake further investigation of these risks, also assessing the behaviour of other COVID-19 vaccines. Close monitoring of the safety of reports of blood clotting disorders will continue, and further studies are underway to provide more laboratory data and real-world evidence.

News. COVID-19 Vaccine AstraZeneca: benefits still outweigh the risks despite possible link to rare blood clots with low blood platelets. EMA. 18/03/2021