The blood-clot events with the AstraZeneca and J&J vaccines are so rare—appearing in one in 100,000 to one in 1 million vaccine recipients—that they would not have shown up in clinical trials, even ones conducted within more leisurely, non-pandemic timelines. (The COVID-19 vaccine trials, which generally included tens of thousands of participants each, were actually unusually large because researchers wanted data as quickly as possible.) “It’s true with all new medications of any sort. You only find rare events when things are rolled out to very vast numbers of people,” says John Grabenstein, the associate director of scientific communication for the Immunization Action Coalition, who used to work on vaccines for the pharmaceutical giant Merck. “One-in-a-million events are just barely measurable.” That faint signal is especially difficult to see against a noisy background: Some people get blood clots for reasons unrelated to the vaccine, too.
In Europe, the strange nature of these blood clots tipped doctors off to a possible link to AstraZeneca’s vaccine. The patients with clots also had low numbers of platelets, which are tiny blood cells that help with clotting. Normally, someone with a low platelet count cannot form clots and bleeds as a result. But in these people, who had all recently gotten an AstraZeneca shot, an immune reaction may have set off uncontrolled clotting that bound up all their platelets.
Some scientists now hypothesize that the immune reaction is triggered by some part of the adenovirus-vector technology. If that’s true, these blood clots might show up as a rare side effect with other adenovirus-vector vaccines. But they clearly are very infrequent. The AstraZeneca and J&J coronavirus vaccines are the first adenovirus-vector shots to even be deployed widely enough in the U.S. and Europe for such rare events to emerge, but vaccines including Russia’s Sputnik V, China’s CanSino, and J&J’s Ebola vaccine also use the technology.
mRNA vaccines are similarly new, but they have so far racked up a good safety record. So many doses have been administered that these unusual blood clots—or any serious one-in-a-million event—would very likely have shown up by now. Back in December, experts quickly noticed and warned the public about a handful of severe allergic reactions to the Pfizer and Moderna vaccines, which is why vaccination sites now monitor recipients for 15 to 30 minutes after the jab. In addition, doctors have picked up on a possible one-in-a-million risk of a bleeding disorder called immune thrombocytopenia, which happens when the immune system attacks platelets after vaccination. (It’s a rare but documented side effect of some other vaccines, such as the one against measles.) These patients do have low platelet counts, but they do not have the accompanying blood clots that seem unique to adenovirus-vector vaccines.