By Edward Chen
CDC, FDA, and EMA investigating potential link between J&J vaccine and brain blood clots.
EMA concludes “possible link”; CDC and FDA investigation ongoing.
7 US cases of CVST with thrombocytopenia (low platelet counts), resulting in 1 reported death, have been reported.
All cases occurred in women between 18 and 48 years of age, within 3 weeks of receiving the J&J vaccine.
Original 6 cases and 1 death reported by CDC and FDA; 1 additional case reported by media and included in EMA analysis.
1 non-fatal US case of non-CVST thrombosis with thrombocytopenia, in a man during clinical trials, has been reported by media and included in EMA analysis.
First 6 reported cases represent 1 case for every 235,000 women 20-50 years old that have received the J&J vaccine.
COVID-19 has killed 565,000 people in US.
Equivalent of 1,700 deaths per million Americans.
After making a splash as the third, and most recent, COVID-19 vaccine to receive an emergency use authorization (EUA) from the US Food and Drug Administration (FDA), the Johnson and Johnson vaccine has made headlines again. Recently, concern has arisen around several people who developed “rare and severe” blood clots in the brain within 2 weeks of receiving a J&J vaccine, leading to one death. These cases occurred in a tiny fraction of the 7.96 million J&J vaccine doses that have been administered in the US so far. In comparison, over 560,000 Americans have died from COVID-19.
The blood clotting cases led US regulatory agencies to recommend a pause in vaccinations with the J&J vaccine on April 13 even though, at the time, American federal agencies “d[id] not know enough yet to say if the vaccine is related to or caused this health issue.” The European Union agency in charge of evaluating vaccines and other medical products concluded yesterday that the J&J vaccine has a “possible link” to these blood clots, which “should be listed as very rare side effects of the vaccine.”
What is known?
According to an April 14 Centers for Disease Control and Prevention (CDC) presentation, between March 19 and April 12, six cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia were reported to the Vaccine Adverse Event Reporting System (VAERS). VAERS is a database that tracks any symptom following a vaccination - an adverse event in FDA parlance - regardless of whether the symptom is actually caused by the vaccine. This allows the FDA to identify potential side effects and continually assess vaccine safety, even after a federal approval or emergency authorization. “This continuous, robust safety monitoring helps keep COVID-19 vaccines safe and helps ensure the benefits of vaccination continue to outweigh any risks.”
At the time of the presentation, 1 person had died while 3 people remained hospitalized and 2 had been discharged home. All 6 cases occurred within 2 weeks of vaccination in women between 18 and 48. There weren’t other obvious similarities between the cases.
Since April 14, an additional case of CVST with thrombocytopenia, reportedly in a 28-year-old woman, and a case of blood clotting with thrombocytopenia, in a man during the vaccine’s clinical trial, have been reported in the media. Neither the CDC nor the FDA have yet confirmed these two additional blood clotting cases, even though a statement from a European Union agency has referenced “eight cases of thrombosis in combination with thrombocytopenia … in the United States.”
These two newly publicized cases bring the total tally to a likely 7 cases of CVST with thrombocytopenia, all in women, and another case of thrombosis with thrombocytopenia, in a man. At a White House press briefing Monday this week, CDC director Dr. Rochelle Walensky said the CDC and FDA are adjudicating “a handful” of severe adverse events associated with the J&J vaccine, which may increase the number of known blood clotting cases.
What actions have regulatory agencies taken?
On April 13, the FDA and the CDC together announced their recommendation to pause use of the J&J vaccine while they further investigate these rare occurrences. “Out of an abundance of caution,” the two agencies made this recommendation to “review the data from six reported cases in the U.S. of a rare and severe type of blood clot [and] ensure that the health care provider community is aware of the potential for these adverse events and can plan for proper recognition and management due to the unique treatment required with this type of blood clot.” The CDC Advisory Committee on Immunization Practices (ACIP) will meet Friday this week to discuss the J&J vaccine.
Even earlier, on April 9, the European Medicines Agency (EMA) had announced a review into “four serious cases of unusual blood clots with low blood platelets.” The EMA, which is responsible for regulating vaccines and other medicines in the European Union, had granted a conditional marketing authorisation (CMA) to the J&J vaccine on March 11, though the vaccine had not been widely used yet in the EU. Johnson & Johnson decided “to proactively delay the rollout of [their] vaccine in Europe” after the joint FDA and CDC announcement.
Yesterday, on April 20, the EMA concluded that the J&J vaccine is “possibly link[ed] to very rare cases of unusual blood clots with low blood platelets” based on their safety committee’s review of the eight publicly reported cases in the US. The EMA’s safety committee also concluded that thrombosis and thrombocytopenia should be included as a “very rare” side effect that has occurred within 3 weeks of vaccination in the vaccine’s data sheet. The EMA reaffirmed that the benefits of the vaccine continue to outweigh the risks. On the same day, Johnson & Johnson announced a resumption of their EU vaccine rollout.
What is cerebral venous sinus thrombosis (CVST) with thrombocytopenia?
In CVST, blood clots form in the vessels that carry blood out of the brain, sometimes resulting in the leakage of blood into the brain (a form of stroke). Therefore, CVST is not directly comparable with other clotting conditions, such as those caused by birth control pills. The term thrombocytopenia reflects the low level of platelets, a protein essential to blood clotting, that appears with these cases of CVST. The low platelet count is notable because blood clots do not usually present with concurrent low platelet levels. 3 out of the 6 originally reported patients also had additional blood clots in other areas of their body. It’s unknown how exactly these blood clots form, though the EMA has suggested the mechanism is an immune response similar to that seen in heparin-induced thrombocytopenia (HIT), another blood clotting condition.
The cases associated with the J&J vaccine, though clinically similar and identically named, are unrelated to recent but separate concerns of blood clots with another coronavirus vaccine, one developed by the University of Oxford together with AstraZeneca. The Oxford-AstraZeneca vaccine does not have emergency approval in the US and has been investigated by the EMA. The EMA announced on April 7 that the Oxford-AstraZeneca vaccine is linked to “very rare cases of unusual blood clots with low blood platelets,” while reaffirming that the benefits of that vaccine also still outweigh the risks.
Can you put the 6 government-announced blood clotting cases in perspective?
At the time the FDA and CDC announced the original 6 cases, 6.86 million doses of the Johnson and Johnson vaccine had been administered. Thus, 6 blood clotting cases is equivalent to roughly 1 case per 1.14 million doses administered. Because these first-announced 6 cases were in women between 18 and 48, it may also be reasonable to look more specifically at younger women.
Up until April 12, 1.4 million doses were administered to women between 20 and 50. Thus, the 6 cases are approximately equivalent to 1 case for every 235,000 women between 20 and 50 who received the J&J vaccine. This is 3 times greater than the expected baseline rate of CVST, according to the CDC. The incidence rate of CVST has been estimated at anywhere between 1 to 16 cases per million people, with women accounting for 75% of CVST cases. Note that a 3-fold increase in a very small number is also a very small number. In this case, the incidence rate among women who receive the J&J vaccine is a very small 4.3 cases per million. COVID-19 has killed 1,700 out of every 1 million Americans.
The rates of blood clotting are in contrast with the 2 other vaccines that have an EUA in the US. Up until a day before the J&J pause was announced, the Pfizer-BioNTech vaccine had 0 reported VAERS cases with 97.9 million administered doses and the Moderna vaccine had 3 cases of CVST without low platelet counts out of 84.7 million doses injected.
In comparison, out of 25 million people who received the Oxford-AstraZeneca vaccine in the European Economic Area and the UK up to March 22, 2021, the EMA reviewed 62 cases of CVST and 24 cases of splanchnic vein thrombosis. 18 of these cases were fatal. This is anywhere between 1 CVST case per 400,000 vaccinations to 1 case per 800,000 vaccinations, depending on how many people had received a single dose and how many had completed the full course of the two-shot Oxford-AstraZeneca vaccine.
As of April 21, 8 million doses of the J&J vaccine have been administered in the US. This is up 1.14 million from Tuesday last week, when a halt in using J&J vaccines was recommended by the FDA and the CDC. To date, J&J vaccines have accounted for less than 4% of all COVID-19 vaccines administered in the US.
The continued monitoring of the COVID vaccines demonstrates that regulatory agencies remain committed to ensuring that the vaccines are safe and effective, and that the benefits of vaccination continue to outweigh the risks. This should be assuring, rather than disheartening.
The CDC urges you to get vaccinated “as soon as you can.” COVID-19 vaccinations are now open to everybody 16 or older. State health department websites and other useful resources for finding a COVID-19 vaccine are available from the CDC.
Results from ongoing research and the current understanding of COVID-19 are constantly evolving. This post contains information that was last updated on April 21, 2021.