No indication AstraZeneca COVID-19 vaccine causes blood clots - EMA

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) said earlier this week that while its investigation was ongoing, EMA remained of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalisation and death, outweigh the risks of side effects. Accordingly, Hungary did not suspend inoculations with the vaccine developed by AstraZeneca and Oxford University.

The PRAC has on Thursday concluded its preliminary review of a signal of blood clots in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting of 18 March 2021. The Committee confirmed that:

• the benefits of the vaccine in combating the still widespread threat of COVID-19 (which itself results in clotting problems and may 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 (elements in the blood that help it to clot) with or without bleeding, including rare cases of clots in the vessels draining blood from the brain (CVST).

These are rare cases – around 20 million people in the UK and EEA had received the vaccine as of March 16 and EMA had reviewed only 7 cases of blood clots in multiple blood vessels (disseminated intravascular coagulation, DIC) and 18 cases of CVST.

A causal link with the vaccine is not proven, but is possible and deserves further analysis.

Last week, Norway, Bulgaria, Denmark, and Iceland temporarily suspended the use of AstraZeneca’s COVID-19 vaccine, the Netherlands, and Ireland followed suit on Sunday, Italy, Spain, Slovenia, and Germany on Monday, and Sweden and Latvia on Tuesday.

Responding to the wave of suspension, AstraZeneca issued a statement, saying that among 17 million people who have received the vaccine in the EU and the UK, 15 cases of deep-vein thrombosis (DVT) and 22 cases of pulmonary embolism have been reported as of 8 March.

“Many thousands of people develop blood clots annually in the EU for different reasons,” the EMA said in a statement. The number of blood clotting incidents in vaccinated people “seems not to be higher than that seen in the general population”.

Britain's Medicines and Healthcare products Regulatory Agency (MHRA) on Thursday gave its continued backing to AstraZeneca's COVID-19 vaccine, saying the benefits outweighed the risks after finding there had been five cases of a rare brain blood clot among 11 million administered shots.

Britain's medicines regulator said that use of the vaccine should continue while the five reports were investigated, and one official said that the rollout would likely continue even if a link was proved.

“Overall the number of thromboembolic events reported after vaccination, both in studies before licensing and in reports after rollout of vaccination campaigns (469 reports, 191 of them from the EEA), was lower than that expected in the general population.

This allows the PRAC to confirm that there is no increase in overall risk of blood clots. However, in younger patients there remain some concerns, related in particular to these rare cases

, the EMA said.

The Committee’s experts looked in extreme detail at records of DIC and CVST reported from Member States, 9 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.

However, based on pre-COVID figures it was calculated that less than 1 reported case of DIC might have been expected by 16 March among people under 50 within 14 days of receiving the vaccine, whereas 5 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 12. A similar imbalance was not visible in the older population given the vaccine.

The Committee 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 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 healthcare professionals of their recent vaccination. Steps are already being taken to update the product information for the vaccine to include more information on these risks.

The PRAC will undertake additional review of these risks, including looking at the risks with other types of COVID-19 vaccines (although no signal has been identified from monitoring so far).

Close safety monitoring of reports of blood clotting disorders will continue, and further studies are being instituted to provide more laboratory data as well as real-world evidence.  EMA will communicate further as appropriate.

Information for patients

1. COVID-19 Vaccine AstraZeneca is not associated with an increased overall risk of blood clotting disorders.
2. There have been very rare cases of unusual blood clots accompanied by low levels of blood platelets (components that help blood to clot) after vaccination. The reported cases were almost all in women under 55.
3. Because COVID-19 can be so serious and is so widespread, the benefits of the vaccine in preventing it outweigh the risks of side effects.

However, if you get any of the following after receiving the COVID-19 Vaccine AstraZeneca:

• breathlessness,
• 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,

please seek prompt medical assistance and mention your recent vaccination.