The COVID-19 vaccines have now protected millions of people from infection, teaching their immune systems to make beneficial antibodies and other customized defenses against the coronavirus.

But in extremely rare cases, the vaccine made by Johnson & Johnson may stimulate production of a second, harmful type of antibody — an autoimmune response that sets off a cascade of blood clots. With the discovery of six such cases in the United States out of more than six million recipients, regulators on Tuesday recommended a pause in administering that vaccine while scientists raced to solve the puzzle.

The worrisome phenomenon may be linked to the delivery system for the J&J vaccine: a different type of virus called an adenovirus. In Europe and in other countries, similar, rare cases of blood clots have been identified in people who received another adenovirus-based COVID-19 vaccine, made by AstraZeneca.

“I think that’s what is happening here. It may be an immune response to the adenovirus,” said Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and an adviser to the Food and Drug Administration.

» READ MORE: How the J&J pause upended plans and sparked concern across the Philly region.

But after a pause, European countries are using the AstraZeneca vaccine once again, after regulators concluded that its benefits in an ongoing pandemic outweighed any possible risk of clots. A U.S. advisory board is scheduled to undertake a similar risk-reward calculation in a public meeting Wednesday.

In the meantime, no such clots have been identified in the many millions who have received either of the RNA vaccines — one made by Moderna, the other by Pfizer and BioNTech SE — and regulators urged people to keep signing up for them.

In a media briefing, acting FDA Commissioner Janet Woodcock said the J&J pause was a sign that the system works, as the clots were discovered through careful monitoring for adverse events.

“We are committed to vaccination,” she said. “We also are committed to patient safety.”

In a statement, the drugmaker said it was working closely with regulators.

“At present, no clear causal relationship” has been identified between the blood clots and the vaccine, the company said. “We strongly support the open communication of this information to healthcare professionals and the public.”

» READ MORE: How the Johnson & Johnson vaccine works

The key actors in this story are platelets: microscopic, cell-like discs in the bloodstream that help to form beneficial blood clots — starting off the healing process in an injured blood vessel by gathering to form a “plug.”

But in six recipients of the J&J vaccine and in dozens who got the AstraZeneca injections, the clotting system kicked into gear when no injury was present.

Evidence suggests that the trigger was an autoimmune response, in which the patients’ antibodies somehow activated the platelets circulating in their bloodstreams, causing them to aggregate, European scientists wrote recently in the New England Journal of Medicine.

All six of the U.S. patients developed clots in veins that drain blood from the brain, and one died. Another is in critical condition in a Nebraska hospital, according to federal officials. Some of the European patients experienced similar stroke-like clots, as well as clots elsewhere in the body.

While the phenomenon remains poorly understood, it resembles a type of abnormal clotting that occurs, paradoxically, in people who are being given a drug to prevent clots: the blood thinner heparin, said Steven E. McKenzie, chief of the hematology service at Thomas Jefferson University Hospital.

So for now, U.S. health officials are recommending that heparin not be used in people who have blood clots after getting the J&J vaccine, lest that make the problem worse. But McKenzie cautioned that the science was unclear.

“We just don’t know why certain people are capable of having the immune response going in the wrong direction,” he said.

The blood clots in the vaccine recipients were so extensive that their platelets were “used up,” their levels declining measurably in the bloodstream, McKenzie said. The same combination of dangerous blood clots and low levels of platelets was identified in recipients of the AstraZeneca vaccine.

The six U.S. patients all were women, with initial symptoms — such as abdominal pain, leg pain, severe headache, and shortness of breath — starting six to 13 days after vaccination. Federal health officials stressed that this cluster of symptoms was distinct from the benign variety of post-vaccine headache that many experience within a day of vaccination.

The advisory panel that meets Wednesday is a committee of the U.S. Centers for Disease Control and Prevention. Among other data points, members will balance the apparent risk of clots — one in one million — with the indisputably higher risk of complications in people who become ill with COVID-19.

In people aged 18 to 49, for example, 1 in 2,000 people infected with the coronavirus will die of the disease, according to the CDC, and a significant portion of those who survive suffer lasting consequences. And the rates of death and severe complications grow higher with age.

All six women with the clots were aged 18 to 48, though some European patients did not meet that description. That suggests three possible courses of action for the federal vaccine advisory committee that meets Wednesday, said Offit, the Children’s Hospital physician:

The committee could conclude the J&J vaccine’s benefits outweigh the risks, as European regulators did with AstraZeneca. The committee could recommend restricting the vaccine to those who seem to be at low or no risk of clots, say, men over 50. Or the panel could urge shelving the J&J vaccine, he said.

“For this country, the calculation is different because we have two other vaccines,” he said. “If J&J is out of the picture, will it significantly delay our ability to get control of the virus? If not, then you could reasonably say we don’t need it.”

Woodcock, the FDA official, was more optimistic.

“We expect it to be a matter of days for this pause,” she said.