The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) completed the review of AstraZeneca’s COVID-19 vaccine. The review was carried out in the light of post-vaccination reports of thromboembolic events and other conditions related to blood clots.
At its extraordinary meeting of 18 March 2021, PRAC confirmed that:
- the benefits of the vaccine in combating the widespread threat of COVID-19 (which itself results in clotting problems and can be fatal) continue to outweigh the risk of side effects;
- the vaccine is not associated with an increase in the overall risk of blood clots (thromboembolic events) in those who receive it;
- there is no evidence of a problem related to specific batches of the vaccine or to particular manufacturing sites;
- however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e. low levels of blood platelets (cells that help blood to clot) with or without bleeding, including rare cases of clots in the vessels draining blood from the brain (cerebral venous sinus thrombosis, CVST).
These are rare cases – around twenty million people in the UK and EEA had received the vaccine as of 16 March 2021 – and EMA had reviewed only seven cases of blood clots in multiple blood vessels (disseminated intravascular coagulation, DIC) and eighteen cases of CVST. A causal link with the vaccine is not proven, but is possible and deserves further analysis.
PRAC involved experts in blood disorders in its review, and worked closely with other health authorities including the British medicines agency MHRA, that has experience with administration of this vaccine to around eleven million people. Overall, the number of thromboembolic events reported after vaccination, both in studies before marketing and in reports after rollout of vaccination campaigns (469 reports, 191 of them from the EEA), was lower than expected in the general population. This allows PRAC to confirm that there is no increase in overall risk of blood clots. However, in younger patients there remain some concerns, particularly related to these rare cases.
PRAC's experts looked in detail at records of DIC and CVST reported from Member States, nine of which resulted in death. Most of these occurred in people under 55 and the majority were women. Because these events are rare, and COVID-19 itself often causes blood clotting disorders in patients, it is difficult to estimate a background rate for these events in people who have not had the vaccine. Based on pre-COVID figures, it was calculated that less than one reported case of DIC might have been expected by 16 March 2021 among people under 50 within fourteen days of receiving the vaccine, whereas five cases had been reported. Similarly, on average 1.35 cases of CVST might have been expected among this age group whereas by the same cut-off date there had been twelve. A similar imbalance was not visible in the older population given the vaccine.
PRAC was of the opinion that the vaccine's proven efficacy in preventing hospitalisation and death from COVID-19 outweighs the extremely small likelihood of developing DIC or CVST. However, in the light of these findings, patients should be aware of the low risk of such symptoms and, if symptoms suggest coagulation problems, patients should seek immediate medical attention and inform the doctor of their recent vaccination. Steps are already being taken to update the product information for the vaccine to include more information on these risks.
PRAC will undertake additional review of the risks of DIC and CVST after receiving the COVID-19 Vaccine AstraZeneca, including looking at the risks with other types of COVID-19 vaccines (although no signal has been identified so far). Reports of blood clotting disorders will continue to be closely monitored, and further studies will be launched to obtain more laboratory and field data. EMA will communicate further as appropriate.
Information for patients
- COVID-19 Vaccine AstraZeneca is not associated with an increased overall risk of blood clotting disorders.
- There have been very rare cases of unusual blood clots accompanied by low levels of blood platelets (cells that help blood to clot) after vaccination. Most of the cases reported have occurred in women under 55.
- The benefits of the vaccine in preventing it outweigh the risks of side effects, because COVID-19 can be so serious and is so widespread.
- Please seek immediate medical attention and inform your doctor of your recent vaccination, if you get any of the following symptoms after receiving the COVID-19 Vaccine AstraZeneca:
- shortness of breath,
- pain in the chest or stomach,
- swelling or coldness in an arm or leg,
- severe or worsening headache or blurred vision after vaccination,
- persistent bleeding,
- multiple small bruises, reddish or purplish spots, or blood blisters under the skin.
Information for healthcare professionals
- Cases of thrombosis and thrombocytopenia, some presenting as mesenteric vein or cerebral vein/cerebral venous sinus thrombosis, have been reported in persons who had recently received COVID-19 Vaccine AstraZeneca, mostly occurring within two weeks after vaccination. The majority of reports involved women under 55, although some of this may reflect greater exposure of such individuals due to targeting of particular populations for vaccine campaigns in different Member States.
- The number of reported events exceeds those expected, and causality although not confirmed, cannot therefore be excluded. Given the rarity of the events and the difficulty of establishing baseline incidence since COVID-19 itself is resulting in hospitalisations with thromboembolic complications, the strength of any association is uncertain.
- EMA considers that the benefit-risk balance of the medicine remains positive, and there is no association with thromboembolic disorders overall. Steps will be taken to update the summary of product characteristics (SmPC) and package leaflet with information on cases of DIC and CVST that have occurred.
- Healthcare professionals are urged to be alert for possible cases of thromboembolism, DIC or CVST occurring in vaccinated individuals. Recipients should be warned to seek immediate medical attention for symptoms of thromboembolism, and especially signs of thrombocytopenia and cerebral blood clots such as easy bruising or bleeding, and persistent or severe headache, particularly beyond three days after vaccination.
A direct healthcare professional communication (DHPC) will be sent to healthcare professionals prescribing, dispensing or administering the medicine. This information will also be published on the FAMHP website.