After formal review, the World Health Organization (WHO) and the European Medicines Agency (EMA) declared that the benefits of preventing hospitalization and death from COVID-19 outweigh the possible risks of thromboembolic events and thrombocytopenia, which are clearly rare, after receiving AstraZeneca’s COVID-19 vaccine.
The statements come after 13 European countries put vaccinations with the AstraZeneca shot on hold in recent days. Other countries suspended use of certain batches of the vaccine, following reports of rare blood clotting disorders and bleeding among people who had received the vaccine.
As of March 16, about 20 million people across Britain and Europe had received the AstraZeneca vaccine. Among these, there have been seven reports of disseminated intravascular coagulation (DIC), or widespread formation of blood clots throughout multiple blood vessels in the body, often accompanied by very low blood platelets. Also, 18 people were said to have developed cerebral venous thrombosis (CVT) after receiving the AstraZeneca vaccine. CVT is very rare and affects about 5 people in 1 million every year. It happens when a clot forms in the veins that drain blood from the brain, which can lead to hemorrhage into the brain and stroke.
Almost all of these cases of DIC or CVT after receiving the AstraZeneca vaccine were among women under age 55. Nine of these individuals died, according to the EMA statement.
Both the EMA’s pharmacovigilance and risk assessment committee and the WHO COVID-19 subcommittee of the Global Advisory Committee on Vaccine Safety reviewed safety data on rare thromboembolic events, and determined that a causal relationship cannot be proven at this time.
Both organizations added that the data do not suggest an overall increase in clotting events related to the vaccine, and that the overall number of thromboembolic events reported in studies before and after licensing and during vaccine rollout were actually lower than expected in the general population.
However, the EMA said: “[I]n younger patients there remain some concerns…. 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 CVT 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.”
Both WHO and EMA agreed that further analysis and monitoring is warranted. They added that healthcare providers and patients should be aware of the possibility of these events, and that appropriate education should be provided.
The EMA cautioned that anyone who develops the following symptoms after receiving the AstraZeneca vaccine should seek prompt medical attention and mention their recent vaccination: breathlessness, pain in the chest or stomach, swelling or coldness in an arm or leg, severe or worsening headache, blurred vision, persistent bleeding, multiple small bruises or blood blisters under the skin.
The EMA added that the AstraZeneca product information should be updated to include information on these risks.
Whether or not the cases of CVST and DIC were related to the vaccine is unclear. Rare clotting problems like these are more common among pregnant or postpartum women. Other risk factors include recently starting oral contraceptives, sepsis, cancer, and having an underlying condition that increases the tendency to form clots such as Factor V Leiden deficiency or lupus.
On Friday, two European research groups asserted that they had found a cause — a rogue antibody generated by the vaccine that interacts somehow with platelets — but details were sketchy, with no indication of formal publication or even manuscripts at this time.
COVID-19 infection can also cause problems with clotting, either due to a direct effect of the infection on the lining of blood vessels or because being critically ill can predispose to blood clots, said Louise McCullough, MD, PhD, of the University of Texas Health Science Center at Houston.
“We’ll have to wait and see if this pans out,” she said. “Anytime you see a relatively rare disease and someone’s gotten a new therapy, you have to have a very low index of suspicion. It’s possible the CVTs were triggered by the vaccine, but it could also be that there was something unique about these seven cases that made them more likely to clot. It’s also possible it was just some weird statistical anomaly.”
Acknowledging that he might not know the full story, Jeffrey Berger, MD, of NYU Langone Medical Center in New York City, said, “I think regulatory agencies have an obligation to protect patients. If they need a little time to investigate people who are seemingly healthy and may be at risk from a vaccine, that’s under their jurisdiction.”
Berger is co-primary investigator on the ACTIV-4a trial, which is looking at the role of anti-thrombotics in adults hospitalized with COVID-19.
“The numbers are not overwhelming to me,” he said. “I don’t understand why these countries are putting patients at risk by pausing the use of a vaccine for what appears to be not an extraordinarily [common] adverse event.”