Scientists begin to unravel rare blood clotting disorder connected to J&J and AstraZeneca vaccines

Although still murky, a picture is starting to emerge about the connection between two types of COVID-19 vaccines and rare blood clots.

The Johnson and Johnson vaccine, which has been delivered to more than 6.8 million Americans, has been associated with at least six cases of severe and very uncommon blood clots in women ages 18-48.

“It just doesn’t happen in healthy people out of the blue and that’s what’s happening,” said Dr. Hanny Al-Samkari, a hematologist and clinical investigator at the Massachusetts General Hospital.

In response, the Food and Drug Administration Tuesday called for a pause in the use of the J&J vaccine, pending more research. An advisory committee to the Centers for Disease Control and Prevention is meeting Wednesday afternoon to discuss the problem and make recommendations about how it should be resolved.

Dr. Peter Marks, director of the Center for Biologics Evaluation and Research at the FDA, said he hopes pausing the J&J shots will call attention to vaccine-associated blood clots, helping alert patients and doctors to concerning symptoms and perhaps identifying more cases.

“Obviously the vaccines are tremendously safe. We are talking about 6 events in 6.85 million doses administered,” he said on a Tuesday afternoon webinar sponsored by the American Medical Association.

But the risks are unexpected, unusual and might be reduced with the proper response or by limiting who gets the vaccine, Marks said.

“Our ultimate goal here is to get as many people vaccinated with a safe and effective vaccine as we can,” he said, “but we feel like we have to take action.”

The condition is believed to be the same one seen in Europe with a similar vaccine made by AstraZeneca and Oxford University. That vaccine, which is not available in the United States, has been linked to more than 220 unusual clotting cases as of April 4, out of 34 million doses delivered.

COVID vaccine on April 8, 2021, in New York City.

The shots used most frequently in the United States, one from Moderna and the other from Pfizer and its partner BioNTech, have been delivered more than 185 million times and have not caused clots or any other serious health problem, according to government tracking.

Most of the time, it’s difficult to directly connect a serious health problem with a vaccine, but with the J&J and AstraZeneca-Oxford vaccines, “there is a smoking gun,” said Dr. Theodore Warkentin, who co-authored an April 9 paper describing unusual blood clotting conditions in 11 patients who received the AstraZeneca-Oxford vaccine.

Anyone who develops the condition 1-3 weeks after vaccination, who hasn’t been taking the blood-thinner heparin almost certainly got sick from the vaccine, he said.

Vaccine-induced problems

Warkentin and his colleagues named the condition vaccine-induced immune thrombotic thrombocytopenia or VITT. It is believed to be similar to a rare problem seen either in patients recovering from surgery or from those on heparin, said Warkentin, a hematologist at McMaster University in Ontario, Canada..

In all cases, the immune system creates antibodies that activate platelets in the bloodstream, he said. The platelets, which normally promote wound healing, end up clumping and causing blood clots, often in the brain.

This also leads to low levels of platelets circulating in the bloodstream, which is called thrombocytopenia.

The diagnosis of VITT may be challenging, because typical tests for blood clots can come back negative and doctors will have to look specifically for toxic antibodies, said Anand Padmanabhan, an expert in a similar condition called heparin-induced thrombocytopenia at the Mayo Clinic.

Padmanabhan said he agreed with the FDA’s pause, to allow a better understanding of the condition and how to detect and treat it.

There is no way, Padmanabhan said, to predict who will develop unusual blood clotting problems. “You can’t profile somebody and say ‘you’re likely to get this,'” he said.

VITT seems to occur 5-13 days after vaccination with the J&J or AstraZeneca-Oxford shots – after the normal vaccine side effects have abated.

Anyone who develops an unusual or severe headache during this time, severe abdominal pain or a painful, swollen leg, possibly accompanied by a skin rash of tiny reddish-purple spots, should seek immediate medical attention, Marks said.

People with suspected VITT should not be given the blood thinner heparin, because it could exacerbate the problem, Padmanabhan said.

All six of the people diagnosed with rare clots after receiving the J&J vaccine were relatively young women – but that doesn’t mean that men and people who are older can’t develop the condition, Marks warned.

Cars full of people wanting a COVID-19 vaccine line up in the parking lot of Autzen Stadium on March 27.

During a large clinical trial in the United States, one man developed similar symptoms, Marks said, so it’s not clear whether VITT is more likely to happen in women, or if the higher rates are merely coincidence.

It’s also possible that the condition appeared more often in young women because they were more likely to get the AstraZeneca-Oxford and J&J vaccines, said Dr. Jean Connors, a hematologist at Brigham and Women’s Hospital in Boston.

“It’s a question of whether this is the tip of the iceberg,” she said. “Are we just seeing the start of case reports in the U.S. and are we going to see more?”

What can be done?

About 1-2% of hospitalized patients given the drug heparin end up withheparin-induced thrombocytopenia, or HITT, which is very similar to VITT, said Al-Samkari,from Massachusetts General Hospital.

It’s impossible to figure out ahead of time who is likely to get the reaction to heparin, and when it’s triggered by an autoimmune reaction, so-called aHIT, it can be particularly bad, he said. “Clots can form everywhere,” he said.

Connors, who has been responsible for treating HITT patients at the Brigham for a decade, said the condition is very risky.

“If you mistreat it, people die,” she said, “and if you don’t treat it, there’s still a high mortality associated with it.”

But it can be successfully treated if doctors are looking for it.

“If you’re not aware it can happen or you’re not looking for it, it may go undiagnosed,” she said.

Blood thinning drugs other than heparin can be useful for VITT patients, Warkentin said.

Padmanabhan discovered that high-dose intravenous immunoglobulin, often called IVIG, can help treat immune reactions. One patient he treated who had the autoimmune version of the disease was slated to have both lower legs amputated, but Padmanabhan was able to save the legs by giving him IVIG.

IVIG coats platelets with normal antibodies, Padmanabhan said, preventing toxic antibodies from damaging the platelets.

The FDA might also limit the J&J and AstraZeneca-Oxford vaccines to certain groups of people, although it’s not yet clear which groups would be most appropriate, said Al-Samkari.

All of the vaccines deliver to the immune system the so-called spike protein found on the surface of the virus that causes COVID-19. Both the J&J and AstraZeneca-Oxford vaccines use harmless viruses to deliver that protein – suggesting that the virus or the DNA it carries is likely triggering the immune overreaction, Al-Samkari said.

Many low- and middle-income countries had pinned their hopes on the AstraZeneca-Oxford vaccine, because it is less expensive and easier to store than the two vaccines that have been used on most Americans.

It’s not yet clear what the blood clotting problems will mean – if anything – in those countries. Padmanabhan, who is a native of India, said there have been no cases of VITT identified in India despite being widely used there. He doubts that’s due to underreporting, though it’s possible, or perhaps because of some genetic difference between people of European versus Indian ancestry.

All of the researchers said they hope the very rare events and the FDA’s reaction won’t make people more nervous about getting the vaccine.

Marks said he’s optimistic that the FDA’s openness and swift action will build trust in the system – and help people realize that the vaccines that haven’t been flagged truly are safe.

Al-Samkari said he reassured his patients Tuesday by telling them that the system is working the way it’s supposed to.

“Whenever there is a concern about the vaccine, they put a hold on it,” Al-Samkari said. “That’s appropriate and we want that to happen.”

Contact Karen Weintraub at kweintraub@usatoday.com.

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.

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